Journal articles: 'Αvβ5'

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LUDBROOK, Steven B., Simon T. BARRY, Chris J. DELVES, and Carmel M. T. HORGAN. "The integrin alphavbeta3 is a receptor for the latency-associated peptides of transforming growth factors beta1 and beta3." Biochemical Journal 369, no. 2 (January 15, 2003): 311–18. http://dx.doi.org/10.1042/bj20020809.

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The integrins αvβ1, αvβ5, αvβ6 and αvβ8 have all recently been shown to interact with the RGD motif of the latency-associated peptide (LAPβ1) of transforming growth factor β1 (TGFβ1), with binding to αvβ6 and αvβ8 leading to TGFβ1 activation. Previously it has been suggested that the remaining αv integrin, αvβ3, does not interact with LAPβ1. However, here we show clearly that αvβ3 does indeed interact with the LAPβ1 RGD motif. This interaction is similar to other αvβ3 ligands in terms of the cations required for adhesion, the concentrations of LAPβ1 required for binding and the ability of a small-molecule inhibitor of αvβ3, SB223245, to block the interaction. Using glutathione S-transferase fusion proteins we have mapped a minimal integrin-binding loop in LAPβ1 and then used this approach to probe the integrin-binding properties of the equivalent loops in LAPβ2 and LAPβ3. We show that the RGD motif of LAPβ3 also interacts with αvβ3, in addition to αvβ6, αvβ1 and αvβ5, whereas the corresponding loop in LAPβ2 does not interact with these integrins. These observations therefore correct a previously reported inaccuracy in the literature. Furthermore, they are important as they link αvβ3 and TGFβ, which may have implications in cancer and a number of inflammatory and fibrotic diseases where expression of both proteins has been documented.

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Seker, Aşkın, Özlem Yildirim, Özlem Kurtkaya, Aydin Sav, Murat Günel, M. Necmettin Pamir, and Türker Kılıç. "Expression of Integrins in Cerebral Arteriovenous and Cavernous Malformations." Neurosurgery 58, no. 1 (January 1, 2006): 159–68. http://dx.doi.org/10.1227/01.neu.0000192174.55131.09.

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Abstract OBJECTIVE: To assess and compare levels and patterns of expression for integrins αvβ1, αvβ3, and αvβ5 in arteriovenous malformations (AVMs) and cavernous malformations (CCMs) of the brain. MATERIALS AND METHODS: Specimens from 10 AVM and 10 CCM lesions were selected from 112 patients with AVMs and 97 patients with CCMs who were treated microsurgically in the Department of Neurosurgery, Marmara University, Istanbul, Turkey. Sections were immunohistochemically stained with antibodies for integrins αvβ1, αvβ3, and αvβ5. Separate histological layers of the vascular wall were evaluated, and levels of expression were graded using a four-tier system. RESULTS: Integrin αvβ1 was more strongly expressed in AVMs than in CCMs. This difference was most pronounced in the endothelium and subendothelium/media. Integrin αvβ3 was more strongly expressed in CCM endothelium than in AVM endothelium (average grades, 0.9 and 0.4, respectively). All 10 of the CCM lesions expressed integrin αvβ5 in the endothelium, whereas only five of the AVMs showed minimal expression of this molecule in the endothelium. CONCLUSION: Current scientific understanding of the roles integrins play in angiogenesis is far from complete. The levels and patterns of expression for these molecules in the histological layers of the vascular walls of AVMs and CCMs provide some clues about the complex biological activities of integrins in these lesions. If one accepts the premise that immunohistochemistry has its inherent methodological problems, integrins αvβ1, αvβ3, and αvβ5 are expressed in AVMs and CCMs in different ways that may be linked to stages of angiogenic maturation. Integrin αvβ1 is expressed more strongly in endothelium and subendothelium/media of AVMs than in the corresponding layers of CCMs. Integrins αvβ3 and αvβ5 are expressed more strongly in CCM endothelium than in AVM endothelium. In addition, integrin αvβ5 staining was stronger in CCM subendothelium than AVM subendothelium/media.

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Berghoff, Anna Sophie, Orsolya Rajky, Frank Winkler, Michael Weller, Christoph Zielinski, Jens Schittenhelm, and Matthias Preusser. "Evaluation of invasion patterns and their correlation with integrin alphavbeta expression in brain metastases of solid cancers." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 2059. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.2059.

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2059 Background: Understanding the pathobiology of brain metastases (BM) could guide the establishment of new targeted therapies. Methods: We collected 57 autopsy specimens of BM (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 1 kidney cancer, 2 colorectal cancer, 13 other) and histologically evaluated the patterns of invasion into the surrounding brain parenchyma. Expression of the following integrins was evaluated using immunohistochemistry: with novel antibodies for αv subunit, αvβ3, αvβ5, αvβ6 and αvβ8 integrin. Results: We observed three main invasion patterns: well-demarcated (29/57, 51%), vascular co-option (10/57, 18%) and diffuse infiltration (18/57, 32%). There was no association of invasion pattern with primary tumor type, although vascular co-option was most common in melanomas (4/10, 40%). αv subunit expression was lowest in the vascular co-option group (p = 0.05, t-test). αvβ6 levels were higher in the well-demarcated group than in the vascular co-option group (p = 0.025; t-test) and were higher in lung cancer BM than in melanoma BM (0.01, t-test). αvβ3 and αvβ5 were frequently expressed in tumoral (αvβ3: 30/57, 53%; αvβ5: 55/57, 97%) and peritumoral (αvβ3: 29/57, 51%, αvβ5: 54/57 (95%) vascular structures and 27/57 (47%) specimens showed avb5 and 6/57 (11%) αvβ3 expression on tumor cells. Prior radio- or chemotherapy did not correlate with invasion pattern or integrin expression. Conclusions: We delineate three distinct invasion patterns of BM into the brain parenchyma: well-demarcated growth, vascular co-option and diffuse infiltration. Integrin expression is frequent on tumor and vascular cells in BM and associated with distinct invasion patterns. Anti-integrin therapy could be a valid treatment option in patients with BM.

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Duque, Hernando, and Barry Baxt. "Foot-and-Mouth Disease Virus Receptors: Comparison of Bovine αV Integrin Utilization by Type A and O Viruses." Journal of Virology 77, no. 4 (February 15, 2003): 2500–2511. http://dx.doi.org/10.1128/jvi.77.4.2500-2511.2003.

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ABSTRACT Three members of the αV integrin family of cellular receptors, αVβ1, αVβ3, and αVβ6, have been identified as receptors for foot-and-mouth disease virus (FMDV) in vitro. The virus interacts with these receptors via a highly conserved arginine-glycine-aspartic acid (RGD) amino acid sequence motif located within the βG-βH (G-H) loop of VP1. Other αV integrins, as well as several other integrins, recognize and bind to RGD motifs on their natural ligands and also may be candidate receptors for FMDV. To analyze the roles of the αV integrins from a susceptible species as viral receptors, we molecularly cloned the bovine β1, β5, and β6 integrin subunits. Using these subunits, along with previously cloned bovine αV and β3 subunits, in a transient expression assay system, we compared the efficiencies of infection mediated by αVβ1, αVβ3, αVβ5, and αVβ6 among three strains of FMDV serotype A and two strains of serotype O. While all the viruses could infect cells expressing these integrins, they exhibited different efficiencies of integrin utilization. All the type A viruses used αVβ3 and αVβ6 with relatively high efficiency, while only one virus utilized αVβ1 with moderate efficiency. In contrast, both type O viruses utilized αVβ6 and αVβ1 with higher efficiency than αVβ3. Only low levels of viral replication were detected in αVβ5-expressing cells infected with either serotype. Experiments in which the ligand-binding domains among the β subunits were exchanged indicated that this region of the integrin subunit appears to contribute to the differences in integrin utilizations among strains. In contrast, the G-H loops of the different viruses do not appear to be involved in this phenomenon. Thus, the ability of the virus to utilize multiple integrins in vitro may be a reflection of the use of multiple receptors during the course of infection within the susceptible host.

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Bodero, Lizeth, Paula López Rivas, Barbara Korsak, Torsten Hechler, Andreas Pahl, Christoph Müller, Daniela Arosio, Luca Pignataro, Cesare Gennari, and Umberto Piarulli. "Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting." Beilstein Journal of Organic Chemistry 14 (February 14, 2018): 407–15. http://dx.doi.org/10.3762/bjoc.14.29.

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RGD-α-amanitin and isoDGR-α-amanitin conjugates were synthesized by joining integrin ligands to α-amanitin via various linkers and spacers. The conjugates were evaluated for their ability to inhibit biotinylated vitronectin binding to the purified αVβ3 receptor, retaining good binding affinity, in the same nanomolar range as the free ligands. The antiproliferative activity of the conjugates was evaluated in three cell lines possessing different levels of αVβ3 integrin expression: human glioblastoma U87 (αVβ3+), human lung carcinoma A549 (αVβ3−) and breast adenocarcinoma MDA-MB-468 (αVβ3−). In the U87, in the MDA-MB-468, and partly in the A549 cancer cell lines, the cyclo[DKP-isoDGR]-α-amanitin conjugates bearing the lysosomally cleavable Val-Ala linker were found to be slightly more potent than α-amanitin. Apparently, for all these α-amanitin conjugates there is no correlation between the cytotoxicity and the expression of αVβ3 integrin. To determine whether the increased cytotoxicity of the cyclo[DKP-isoDGR]-α-amanitin conjugates is governed by an integrin-mediated binding and internalization process, competition experiments were carried out in which the conjugates were tested with U87 (αVβ3+, αVβ5+, αVβ6−, α5β1+) and MDA-MB-468 (αVβ3−, αVβ5+, αVβ6+, α5β1−) cells in the presence of excess cilengitide, with the aim of blocking integrins on the cell surface. Using the MDA-MB-468 cell line, a fivefold increase of the IC50 was observed for the conjugates in the presence of excess cilengitide, which is known to strongly bind not only αVβ3, but also αVβ5, αVβ6, and α5β1. These data indicate that in this case the cyclo[DKP-isoDGR]-α-amanitin conjugates are possibly internalized by a process mediated by integrins different from αVβ3 (e.g., αVβ5).

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Rowedder, James E., Steve B. Ludbrook, and Robert J. Slack. "Determining the True Selectivity Profile of αv Integrin Ligands Using Radioligand Binding: Applying an Old Solution to a New Problem." SLAS DISCOVERY: Advancing the Science of Drug Discovery 22, no. 8 (April 17, 2017): 962–73. http://dx.doi.org/10.1177/2472555217703908.

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The arginyl-glycinyl-aspartic acid (RGD) integrin subfamily contains five members that partner with the αv subunit: αvβ1, αvβ3, αvβ5, αvβ6, and αvβ8. Within the αv integrins, the epithelially restricted αvβ6 has been identified as playing a key role in the activation of transforming growth factor β that is hypothesized to be pivotal in the development of idiopathic pulmonary fibrosis (IPF). As part of a drug discovery program to identify a selective αvβ6 RGD mimetic for IPF, cell adhesion and radioligand binding assays were investigated to screen compounds to determine affinity and αv integrin selectivity. In this study, a pan-αv radioligand was characterized against all the αv integrins and used to determine accurate selectivity profiles for literature and novel RGD ligands, as well as enable an early readout on αvβ6 dissociation kinetics. It has been shown that while cell adhesion offers a high throughput and reliable format for ranking compounds, there are downsides to this format when comparing selectivity across αv integrins. By accurately defining the relationship between these assay formats, a medicinal chemistry effort has identified novel, high-affinity, and selective αvβ6 RGD mimetics with slow dissociation kinetics, with the potential to be developed into clinical candidates for IPF.

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Triantafilou, Kathy, Martha Triantafilou, Yoshikazu Takada, and Nelson Fernandez. "Human Parechovirus 1 Utilizes Integrins αvβ3 and αvβ1 as Receptors." Journal of Virology 74, no. 13 (July 1, 2000): 5856–62. http://dx.doi.org/10.1128/jvi.74.13.5856-5862.2000.

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ABSTRACT Human parechovirus 1 (HPEV1) displays an arginine-glycine-aspartic acid (RGD) motif in the VP1 capsid protein, suggesting integrins as candidate receptors for HPEV1. A panel of monoclonal antibodies (MAbs) specific for integrins αvβ3, αvβ1, and αvβ5, which have the ability to recognize the RGD motif, and also a MAb specific for integrin α2β1, an integrin that does not recognize the RGD motif, were tested on A549 cells. Our results showed that integrin αv-specific MAb reduced infectivity by 85%. To specify which αv integrins the virus utilizes, we tested MAbs specific to integrins αvβ3 and αvβ1 which reduced infectivity significantly, while a MAb specific for integrin αvβ5, as well as the MAb specific for α2β1, showed no reduction. When a combination of MAbs specific for integrins αvβ3 and αvβ1 were used, virus infectivity was almost completely inhibited; this shows that integrins αvβ3 and αvβ1 are utilized by the virus. We therefore proceeded to test whether αv integrins' natural ligands fibronectin and vitronectin had an effect on HPEV1 infectivity. We found that vitronectin reduced significantly HPEV1 infectivity, whereas a combination of vitronectin and fibronectin abolished infection. To verify the use of integrins αvβ3 and αvβ1 as HPEV1 receptors, CHO cells transfected and expressing either integrin αvβ3 or integrin αvβ1 were used. It was shown that the virus could successfully infect these cells. However, in immunoprecipitation experiments using HPEV1 virions and allowing the virus to bind to solubilized A549 cell extract, we isolated and confirmed by Western blotting the αvβ3 heterodimer. In conclusion, we found that HPEV1 utilises both integrin αvβ3 and αvβ1 as receptors; however, in cells that express both integrins, HPEV1 may preferentially bind integrin αvβ3.

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Finnemann, Silvia C., and Enrique Rodriguez-Boulan. "Macrophage and Retinal Pigment Epithelium Phagocytosis." Journal of Experimental Medicine 190, no. 6 (September 20, 1999): 861–74. http://dx.doi.org/10.1084/jem.190.6.861.

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Noninflammatory monocyte macrophages use αvβ3 integrin to selectively bind apoptotic cells, initiating their phagocytic removal. In a related process, the retinal pigment epithelium (RPE) employs αvβ5 integrin to recognize spent photoreceptor outer segment particles (OS). Here, we show that apoptotic cells and OS compete for binding to these receptors, indicating that OS and apoptotic cells expose surface signals recognizable by αvβ3 and αvβ5. Particle binding to αvβ5 required protein kinase C (PKC) activation. In RPE, αvβ5 binding was maximally activated even before any phagocytic challenge and was reduced by PKC inhibitors. In macrophages, it was dormant but became activated upon PKC stimulation. PKC-activated αvβ5-mediated binding in macrophages differed from constitutive binding to the same integrin receptor in RPE cells in that the former followed much faster kinetics, similar to particle binding mediated by αvβ3. Activation of αvβ5 for particle binding correlated with its recruitment into a detergent-insoluble fraction, a process sensitive to pharmacological modulation of PKC in both types of phagocytes. Furthermore, αvβ5 but not αvβ3 particle binding required actin microfilaments. These data constitute the first evidence that noninflammatory phagocytes actively regulate the earliest phase of phagocytic clearance, particle binding, by controlling receptor activity.

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Bello, Lorenzo, Jianping Zhang, Demetrios C. Nikas, Jon F. Strasser, Roberto M. Villani, David A. Cheresh, Rona S. Carroll, and Peter McL Black. "αvβ3 and αvβ5 Integrin Expression in Meningiomas." Neurosurgery 47, no. 5 (November 1, 2000): 1185–95. http://dx.doi.org/10.1097/00006123-200011000-00035.

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Abstract OBJECTIVE Integrins are emerging as alternative receptors capable of mediating several biological functions, such as cell-matrix and cell-cell adhesion, cell migration, signal transduction, and angiogenesis. Two αv integrins, i.e., αvβ3 and αvβ5, play critical roles in mediating these activities, particularly in tumors. No data are available on the expression of these integrins in meningiomas. METHODS Using Western blot and immunohistochemical analyses with LM609 and PG32, two monoclonal antibodies capable of recognizing the functional integrin heterodimer, we evaluated the expression of αvβ3 and αvβ5 integrins in a series of 34 meningiomas of different histological subtypes and grades. We studied their expression in tumor cells and vasculature, as well as the expression of their related angiogenic factors (fibroblast growth factor 2 and vascular endothelial growth factor) and the αvβ3 ligand vitronectin. RESULTS αvβ3 and αvβ5 integrins were expressed by neoplastic vasculature and cells. αvβ3 and αvβ5 expression was associated and correlated with that of their respective growth factors (fibroblast growth factor 2 and vascular endothelial growth factor) and microvessel counts and densities. αvβ3 was more strongly expressed than αvβ5 in two cases of histologically benign meningiomas with aggressive clinical behavior. αvβ3 expression was associated with that of its related ligand vitronectin and was also evident in small vessels of brain tissue closely surrounding meningiomas. CONCLUSION Our data demonstrate the expression of αvβ3 and αvβ5 integrins in meningioma cells and vasculature. Our findings suggest a role for both of these integrins, and particularly αvβ3, in meningioma angiogenesis.

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Janes, Sam M., and Fiona M. Watt. "Switch from αvβ5 to αvβ6 integrin expression protects squamous cell carcinomas from anoikis." Journal of Cell Biology 166, no. 3 (August 2, 2004): 419–31. http://dx.doi.org/10.1083/jcb.200312074.

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Stratified squamous epithelia express the αvβ5 integrin, but in squamous cell carcinomas (SCCs) there is down-regulation of αvβ5 and up-regulation of αvβ6. To investigate the significance of this finding, we transduced an αv-negative human SCC line with retroviral vectors encoding αv integrins. αvβ5-expressing cells underwent suspension-induced apoptosis (anoikis), whereas αv-negative cells and cells expressing αvβ6 did not. Resistance to anoikis correlated with PKB/Akt activation in suspension, but not with changes in PTEN or p110α PI3 kinase levels. Anoikis was induced in parental and αvβ6-expressing cells by inhibiting PI3 kinase. Conversely, activation of Akt or inhibition of caspases in αvβ5-expressing cells suppressed anoikis. Caspase inhibition resulted in increased phosphoAkt, placing caspase activation upstream of decreased Akt activation. Anoikis required the cytoplasmic domain of β5 and was independent of the death receptor pathway. These results suggest that down-regulation of αvβ5 through up-regulation of αvβ6 may protect SCCs from anoikis by activating an Akt survival signal.

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Goodman, Simon L., Günter Hölzemann, Gábor A. G. Sulyok, and Horst Kessler. "Nanomolar Small Molecule Inhibitors for αvβ6, αvβ5, and αvβ3 Integrins." Journal of Medicinal Chemistry 45, no. 5 (February 2002): 1045–51. http://dx.doi.org/10.1021/jm0102598.

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Hood, John D., Ricardo Frausto, William B. Kiosses, Martin A. Schwartz, and David A. Cheresh. "Differential αv integrin–mediated Ras-ERK signaling during two pathways of angiogenesis." Journal of Cell Biology 162, no. 5 (September 1, 2003): 933–43. http://dx.doi.org/10.1083/jcb.200304105.

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Antagonists of αvβ3 and αvβ5 disrupt angiogenesis in response to bFGF and VEGF, respectively. Here, we show that these αv integrins differentially contribute to sustained Ras-extracellular signal–related kinase (Ras-ERK) signaling in blood vessels, a requirement for endothelial cell survival and angiogenesis. Inhibition of FAK or αvβ5 disrupted VEGF-mediated Ras and c-Raf activity on the chick chorioallantoic membrane, whereas blockade of FAK or integrin αvβ3 had no effect on bFGF-mediated Ras activity, but did suppress c-Raf activation. Furthermore, retroviral delivery of active Ras or c-Raf promoted ERK activity and angiogenesis, which anti-αvβ5 blocked upstream of Ras, whereas anti-αvβ3 blocked downstream of Ras, but upstream of c-Raf. The activation of c-Raf by bFGF/αvβ3 not only depended on FAK, but also required p21-activated kinase-dependent phosphorylation of serine 338 on c-Raf, whereas VEGF-mediated c-Raf phosphorylation/activation depended on Src, but not Pak. Thus, integrins αvβ3 and αvβ5 differentially regulate the Ras-ERK pathway, accounting for distinct vascular responses during two pathways of angiogenesis.

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Berghoff, Anna Sophie, Astrid Kerstin Kovanda, Thomas Melchardt, Rupert Bartsch, Johannes A. Hainfellner, Bence Sipos, Jens Schittenhelm, et al. "αvβ3, αvβ5 and αvβ6 integrins in brain metastases of lung cancer." Clinical & Experimental Metastasis 31, no. 7 (August 24, 2014): 841–51. http://dx.doi.org/10.1007/s10585-014-9675-0.

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Wang, Kena, Tinglu Guan, David A. Cheresh, and Glen R. Nemerow. "Regulation of Adenovirus Membrane Penetration by the Cytoplasmic Tail of Integrin β5." Journal of Virology 74, no. 6 (March 15, 2000): 2731–39. http://dx.doi.org/10.1128/jvi.74.6.2731-2739.2000.

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ABSTRACT Adenovirus (Ad) cell entry involves sequential interactions with host cell receptors that mediate attachment (CAR), internalization (αvβ3 and αvβ5), and penetration (αvβ5) of the endosomal membrane. These events allow the virus to deliver its genome to the nucleus. While integrins αvβ3 and αvβ5 both promote Ad internalization into cells, integrin αvβ5 selectively facilitates Ad-mediated membrane permeabilization and endosome rupture. In the experiments reported herein, we demonstrate that the intracellular domain of the integrin β5 subunit specifically regulates Ad-mediated membrane permeabilization and gene delivery. CS-1 melanoma cells expressing a truncated integrin β5 or a chimeric (β5-β3) cytoplasmic tail (CT) supported normal levels of Ad endocytosis but had reduced Ad-mediated gene delivery and membrane permeabilization relative to cells expressing a wild-type integrin β5. Thin-section electron microscopy revealed that virion particles were capable of being endocytosed into cells expressing a truncated β5CT, but they failed to escape cytoplasmic vesicles and translocate to the nucleus. Site-specific mutagenesis studies suggest that a C-terminal TVD motif in the β5CT plays a major role in Ad membrane penetration.

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Li, Erguang, Swati L. Brown, Dwayne G. Stupack, Xose S. Puente, David A. Cheresh, and Glen R. Nemerow. "Integrin αvβ1 Is an Adenovirus Coreceptor." Journal of Virology 75, no. 11 (June 1, 2001): 5405–9. http://dx.doi.org/10.1128/jvi.75.11.5405-5409.2001.

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ABSTRACT The human embryonic kidney (HEK293) cell line, commonly used for recombinant adenovirus (Ad) propagation, does not express the Ad coreceptor αvβ3 or αvβ5 integrins, yet these cells are efficiently infected by Ad vectors. Here we demonstrate that Ad binds to HEK293 cells via the fiber receptor CAR and is subsequently internalized via interaction with integrin αvβ1. Function-blocking antibodies directed against αv or β1, but not β3, β5, or α5, integrin subunits block Ad infection and viral endocytosis. Therefore, αvβ1 serves as a coreceptor for Ad infection, and the lack of β3 and/or β5 but the relatively high expression of αvβ1 integrins on certain tumor cell types may explain why these cells are readily transduced by Ad vectors.

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Friggeri, Arnaud, Yanping Yang, Sami Banerjee, Yong-Jun Park, Gang Liu, and Edward Abraham. "HMGB1 inhibits macrophage activity in efferocytosis through binding to the αvβ3-integrin." American Journal of Physiology-Cell Physiology 299, no. 6 (December 2010): C1267—C1276. http://dx.doi.org/10.1152/ajpcell.00152.2010.

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Phagocytosis of apoptotic cells is critical to resolution of inflammation. High mobility group box 1 protein (HMGB1), a mediator of inflammation, has been shown to diminish phagocytosis through binding to phosphatidylserine (PS) exposed on the surface of apoptotic neutrophils. However, it is currently unknown whether HMGB1 also modulates the activity of receptors involved in PS recognition on the surface of phagocytes. In the present studies, we found that preincubation of macrophages with HMGB1 decreased their ability to engulf apoptotic neutrophils or thymocytes. Preincubation of macrophages with HMGB1 prevented the enhancement of efferocytosis resulting from exposure to milk fat globule EGF factor 8 (MFG-E8), an opsonin that bridges PS and αvβ3 as well as αvβ5-integrins on the surface of phagocytes. The inhibitory effect of HMGB1 on the phagocytic activity of macrophages was prevented by preincubation of HMGB1 with soluble αvβ3, but not with soluble αvβ5. HMGB1 colocalized with the β3-integrin on the cell membrane of macrophages and bound to soluble αvβ3, but not to soluble αvβ5. HMGB1 suppressed the interaction between MFG-E8 and αvβ3. HMGB1 also inhibited intracellular signaling events, including ERK phosphorylation and Rac-1 activation, which are activated in macrophages during phagocytosis of apoptotic cells. These results demonstrate that HMGB1 blocks αvβ3-dependent recognition and uptake of apoptotic cells.

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Veettil, Mohanan Valiya, Sathish Sadagopan, Neelam Sharma-Walia, Fu-Zhang Wang, Hari Raghu, Laszlo Varga, and Bala Chandran. "Kaposi's Sarcoma-Associated Herpesvirus Forms a Multimolecular Complex of Integrins (αVβ5, αVβ3, and α3β1) and CD98-xCT during Infection of Human Dermal Microvascular Endothelial Cells, and CD98-xCT Is Essential for the Postentry Stage of Infection." Journal of Virology 82, no. 24 (October 1, 2008): 12126–44. http://dx.doi.org/10.1128/jvi.01146-08.

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ABSTRACT Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with cell surface heparan sulfate (HS) and α3β1 integrin during the early stages of infection of human dermal microvascular endothelial cells (HMVEC-d) and human foreskin fibroblasts (HFF), and these interactions are followed by virus entry overlapping with the induction of preexisting host cell signal pathways. KSHV also utilizes the amino acid transporter protein xCT for infection of adherent cells, and the xCT molecule is part of the cell surface heterodimeric membrane glycoprotein CD98 (4F2 antigen) complex known to interact with α3β1 and αVβ3 integrins. KSHV gB mediates adhesion of HMVEC-d, CV-1, and HT-1080 cells and HFF via its RGD sequence. Anti-αV and -β1 integrin antibodies inhibited the cell adhesion mediated by KSHV-gB. Variable levels of neutralization of HMVEC-d and HFF infection were observed with antibodies against αVβ3 and αVβ5 integrins. Similarly, variable levels of inhibition of virus entry into adherent HMVEC-d, 293 and Vero cells, and HFF was observed by preincubating virus with soluble α3β1, αVβ3, and αVβ5 integrins, and cumulative inhibition was observed with a combination of integrins. We were unable to infect HT1080 cells. Virus binding and DNA internalization studies suggest that αVβ3 and αVβ5 integrins also play roles in KSHV entry. We observed time-dependent temporal KSHV interactions with HMVEC-d integrins and CD98/xCT with three different patterns of association and dissociation. Integrin αVβ5 interaction with CD98/xCT predominantly occurred by 1 min postinfection (p.i.) and dissociated at 10 min p.i., whereas α3β1-CD98/xCT interaction was maximal at 10 min p.i. and dissociated at 30 min p.i., and αVβ3-CD98/xCT interaction was maximal at 10 min p.i. and remained at the observed 30 min p.i. Fluorescence microscopy also showed a similar time-dependent interaction of αVβ5-CD98. Confocal-microscopy studies confirmed the association of CD98/xCT with α3β1 and KSHV. Preincubation of KSHV with soluble heparin and α3β1 significantly inhibited this association, suggesting that the first contact with HS and integrin is an essential element in subsequent CD98-xCT interactions. Anti-CD98 and xCT antibodies did not block virus binding and entry and nuclear delivery of viral DNA; however, viral-gene expression was significantly inhibited, suggesting that CD98-xCT play roles in the post-entry stage of infection, possibly in mediating signal cascades essential for viral-gene expression. Together, these studies suggest that KSHV interacts with functionally related integrins (αVβ3, α3β1, and αVβ5) and CD98/xCT molecules in a temporal fashion to form a multimolecular complex during the early stages of endothelial cell infection, probably mediating multiple roles in entry, signal transduction, and viral-gene expression.

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Stewart, P. L., C. Y. Chiu, D. Von Seggern, and G. R. Nemerow. "Cryo-Em Imaging of a Pseudotyped Adenovhtus with Ocular Cell Tropism." Microscopy and Microanalysis 6, S2 (August 2000): 286–87. http://dx.doi.org/10.1017/s1431927600033924.

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Human adenovirus (Ad) provides unique model system for studying the multistage events in viral entry. We are applying cryo-electron microscopy and single particle reconstruction methods to study the cell entry pathway of Ad as well as to examine the structure of reengineered Ad vectors. Ad cell entry is mediated by interactions with two different cellular receptors: the fiber receptor, CAR for most Ad serotypes or a 50 kDa receptor for a subset of serotypes including Ad37, for attachment; and the αvβ3 and αvβ5 integrins for internalization. We have previously reconstructed both Ad2 and Adl2 virus particles complexed with a soluble form of αvβ5 integrin. We learned during our comparative cryo-EM study of the Ad2/αvβ5 and Adl2/αvβ5 complexes that the length of the variable RGD loop in the penton base affects the relative height of the integrin density over the penton base.

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Park, Hye Jin, Ji Eun Park, Hyun Lee, Seong Jae Kim, Jung Im Yun, Minseok Kim, Kyu Hyun Park, and Seung Tae Lee. "Integrins functioning in uterine endometrial stromal and epithelial cells in estrus." Reproduction 153, no. 3 (March 2017): 351–60. http://dx.doi.org/10.1530/rep-16-0516.

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Here, as a basic study in the construction of a non-cellular niche that supports artificial organization of three-dimensional endometrial tissue, we defined the types of integrin heterodimers that are expressed transcriptionally, translationally and functionally in endometrial stromal (ES) and endometrial epithelial (EE) cells isolated from the mouse uterus in estrus. Gene and protein expression of integrin subunits were analyzed at the transcriptional and translational level by real-time PCR and fluorescent immunoassay, respectively. Moreover, the functionality of integrin heterodimers was confirmed by attachment and antibody inhibition assays. Itga2, Itga5, Itga6, Itga9, Itgav, Itgb1, Itgb3 and Itgb5 in ES cells, and Itga2, Itga5, Itga6, Itga7, Itga9, Itgav, Itgb1, Itgb3, Itgb4, Itgb5 and Itga6 and in EE cells showed significantly higher transcriptional levels than the other integrin subunits. Furthermore, translational expression of the total integrin α and β subunit genes that showed increased transcription was determined in ES and EE cells. ES cells showed significantly increased adhesion to collagen I, fibronectin and vitronectin, and functional blocking of integrin α2, α5 or αV significantly inhibited adhesion to these molecules. Moreover, EE cells showed significantly increased adhesion to collagen I, fibronectin, laminin and vitronectin, and functional blocking of integrin α2, α5, α6 or αV significantly inhibited adhesion to these molecules. Accordingly, we confirmed that integrin α2β1, α5β1, αVβ1, αVβ3 and/or αVβ5, and integrin α2β1, α5β1, α6β1 and/or α6β4, αVβ1, αVβ3 and/or αVβ5, actively function on the surface of ES and EE cells from mouse uterus in estrus phase, respectively.

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Bello, Lorenzo, Maura Francolini, Paola Marthyn, Jianping Zhang, Rona S. Carroll, Demetrios C. Nikas, Jon F. Strasser, Roberto Villani, David A. Cheresh, and Peter McL Black. "αvβ3 and αvβ5 Integrin Expression in Glioma Periphery." Neurosurgery 49, no. 2 (August 1, 2001): 380–90. http://dx.doi.org/10.1097/00006123-200108000-00022.

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Abstract OBJECTIVE This study analyzed the expression of integrins αvβ3 and αvβ5 in glioma tissue and focused on the periphery of high-grade gliomas. METHODS The analysis was performed with Western blot, immunohistochemistry, and immunofluorescence, by use of two monoclonal antibodies able to recognize the functional integrin heterodimer. The expression of integrin-related ligands and growth factors also was studied. Sections from the tumor periphery were classified as either tumor periphery (light tumor infiltrate or scant visible cells) or peritumor (heavy tumor infiltration). RESULTS Our data on glioma tissues demonstrated that both integrins were expressed in glioma cells and vasculature and their expression correlated with the histological grade. αvβ3 expression was prominent in astrocytic tumors. Both integrins were markers of tumor vasculature, particularly of endothelial proliferation. A high-grade glioma periphery demonstrated a prominent expression of integrin αvβ3. Cells demonstrating αvβ3 positivity were identified as tumor astrocytes and endothelial cells by double imaging. The same cells were surrounded by some αvβ3 ligands and co-localized fibroblast growth factor 2. Matrix metalloproteinase 2 also was found to be co-localized with αvβ3 in the same cells. αvβ3 expression was more relevant in tumor astrocytes. αvβ3 integrin and vascular endothelial growth factor expression increased from the periphery to the tumor center. CONCLUSION Our data support the role of integrins αvβ3 and αvβ5 in glioma-associated angiogenesis. In addition, they suggest a role for integrin αvβ3 in neoangiogenesis and cell migration in high-grade glioma periphery.

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Erdreich-Epstein, Anat, Linda B. Tran, Órla T. Cox, Elaine Y. Huang, Walter E. Laug, Hiroyuki Shimada, and Melissa Millard. "Endothelial apoptosis induced by inhibition of integrins αvβ3 and αvβ5 involves ceramide metabolic pathways." Blood 105, no. 11 (June 1, 2005): 4353–61. http://dx.doi.org/10.1182/blood-2004-08-3098.

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Abstract Matrix ligation of integrins αvβ3/αvβ5 is critical for endothelial survival and angiogenesis. We have previously shown that ceramide, a proapoptotic lipid second messenger, increases during endothelial anoikis (detachment-induced apoptosis). We now show that RGDfV, an integrin αvβ3/αvβ5 cyclic function-blocking peptide, increased ceramide and decreased sphingomyelin in human brain microvascular endothelial cells (HBMECs) plated on vitronectin, suggesting that sphingomyelin hydrolysis contributes to RGDfV-induced ceramide increase. Desipramine and imipramine, inhibitors of acid sphingomyelinase (ASMase), suppressed RGDfV-induced ceramide increase. Importantly, desipramine, imipramine, and a third ASMase inhibitor, SR33557, but not inhibitors of neutral sphingomyelinase, suppressed RGDfV-induced apoptosis, suggesting that ASMase was required for integrin-mediated apoptosis. Myriocin, an inhibitor of de novo ceramide synthesis, had no effect on RGDfV-induced HBMEC apoptosis. Interestingly, ASMase inhibitors also suppressed the RGDfV-induced loss of spreading on vitronectin. RGDfV induced a similar increase in ceramide and apoptosis in HBMECs on poly-l-lysine or vitronectin, although cells detached only from vitronectin, indicating that cell detachment was not required for RGDfV-induced apoptosis. Our results suggest involvement of ASMase and ceramide in endothelial apoptosis induced by inhibition of integrins αvβ3/αvβ5, and propose a novel molecular mechanism for the antiangiogenic effect of RGDfV.

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Cirulli, Vincenzo, Gillian M. Beattie, George Klier, Mark Ellisman, Camillo Ricordi, Vito Quaranta, Francine Frasier, Jennifer K. Ishii, Alberto Hayek, and Daniel R. Salomon. "Expression and Function of αvβ3 and αvβ5 Integrins in the Developing Pancreas." Journal of Cell Biology 150, no. 6 (September 18, 2000): 1445–60. http://dx.doi.org/10.1083/jcb.150.6.1445.

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Cell–cell and cell–matrix interactions play a critical role in tissue morphogenesis and in homeostasis of adult tissues. The integrin family of adhesion receptors regulates cellular interactions with the extracellular matrix, which provides three-dimensional information for tissue organization. It is currently thought that pancreatic islet cells develop from undifferentiated progenitors residing within the ductal epithelium of the fetal pancreas. This process involves cell budding from the duct, migration into the surrounding mesenchyme, differentiation, and clustering into the highly organized islet of Langerhans. Here we report that αvβ3 and αvβ5, two integrins known to coordinate epithelial cell adhesion and movement, are expressed in pancreatic ductal cells and clusters of undifferentiated cells emerging from the ductal epithelium. We show that expression and function of αvβ3 and αvβ5 integrins are developmentally regulated during pancreatic islet ontogeny, and mediate adhesion and migration of putative endocrine progenitor cells both in vitro and in vivo in a model of pancreatic islet development. Moreover, we demonstrate the expression of fibronectin and collagen IV in the basal membrane of pancreatic ducts and of cell clusters budding from the ductal epithelium. Conversely, expression of vitronectin marks a population of epithelial cells adjacent to, or emerging from, pancreatic ducts. Thus, these data provide the first evidence for the contribution of integrins αvβ3 and αvβ5 and their ligands to morphogenetic events in the human endocrine pancreas.

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Bello, Lorenzo, Maura Francolini, Paola Marthyn, Jianping Zhang, Rona S. Carroll, Demetrios C. Nikas, Jon F. Strasser, Roberto Villani, David A. Cheresh, and Peter McL. Black. "αvβ3 and αvβ5 Integrin Expression in Glioma Periphery." Neurosurgery 49, no. 2 (August 2001): 380–90. http://dx.doi.org/10.1227/00006123-200108000-00022.

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Chalier, Florence, Laura Mugnier, Marion Tarbe, Soioulata Aboudou, Claude Villard, Hervé Kovacic, Didier Gigmes, et al. "Isolation of an Anti–tumour Disintegrin: Dabmaurin–1, a Peptide Lebein–1–like, from Daboia mauritanica Venom." Toxins 12, no. 2 (February 5, 2020): 102. http://dx.doi.org/10.3390/toxins12020102.

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In the soft treatment of cancer tumours, consequent downregulation of the malignant tissue angiogenesis constitutes an efficient way to stifle tumour development and metastasis spreading. As angiogenesis requires integrin–promoting endothelial cell adhesion, migration, and vessel tube formation, integrins represent potential targets of new therapeutic anti–angiogenic agents. Our work is a contribution to the research of such therapeutic disintegrins in animal venoms. We report isolation of one peptide, named Dabmaurin–1, from the hemotoxic venom of snake Daboia mauritanica, and we evaluate its potential anti–tumour activity through in vitro inhibition of the human vascular endothelial cell HMECs functions involved in tumour angiogenesis. Dabmaurin–1 altered, in a dose–dependent manner, without any significant cytotoxicity, HMEC proliferation, adhesion, and their mesenchymal migration onto various extracellular matrix proteins, as well as formation of capillary–tube mimics on MatrigelTM. Via experiments involving HMEC or specific cancers cells integrins, we demonstrated that the above Dabmaurin–1 effects are possibly due to some anti–integrin properties. Dabmaurin–1 was demonstrated to recognize a broad panel of prooncogenic integrins (αvβ6, αvβ3 or αvβ5) and/or particularly involved in control of angiogenesis (α5β1, α6β4, αvβ3 or αvβ5). Furthermore, mass spectrometry and partial N–terminal sequencing of this peptide revealed, it is close to Lebein–1, a known anti–β1 disintegrin from Macrovipera lebetina venom. Therefore, our results show that if Dabmaurin–1 exhibits in vitro apparent anti–angiogenic effects at concentrations lower than 30 nM, it is likely because it acts as an anti–tumour disintegrin.

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Lee, Pearl, Daniel V. Bax, Marcela M. M. Bilek, and Anthony S. Weiss. "A Novel Cell Adhesion Region in Tropoelastin Mediates Attachment to Integrin αVβ5." Journal of Biological Chemistry 289, no. 3 (November 29, 2013): 1467–77. http://dx.doi.org/10.1074/jbc.m113.518381.

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Tropoelastin protein monomers assemble to form elastin. Cellular integrin αVβ3 binds RKRK at the C-terminal tail of tropoelastin. We probed cell interactions with tropoelastin by deleting the RKRK sequence to identify other cell-binding interactions within tropoelastin. We found a novel human dermal fibroblast attachment and spreading site on tropoelastin that is located centrally in the molecule. Inhibition studies demonstrated that this cell adhesion was not mediated by either elastin-binding protein or glycosaminoglycans. Cell interactions were divalent cation-dependent, indicating integrin dependence. Function-blocking monoclonal antibodies revealed that αV integrin(s) and integrin αVβ5 specifically were critical for cell adhesion to this part of tropoelastin. These data reveal a common αV integrin-binding theme for tropoelastin: αVβ3 at the C terminus and αVβ5 at the central region of tropoelastin. Each αV region contributes to fibroblast attachment and spreading, but they differ in their effects on cytoskeletal assembly.

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Livnat, Tami, Uri Seligsohn, and Rima Dardik. "Variable effects of alpha v suppression on VEGFR-2 expression in endothelial cells of different vascular beds." Thrombosis and Haemostasis 102, no. 11 (2009): 975–82. http://dx.doi.org/10.1160/th08-10-0687.

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SummaryIntegrins αvβ3 and αvβ5 have been long considered as proangiogenic receptors, yet genetic ablation studies demonstrated enhanced angiogenesis in mice lacking αvβ3 and αvβ5 integrins, which was attributed to increased expression of vascular endothelial growth factor receptor-2 (VEGFR-2). In this study, we determined the effect of αvβ3 and αvβ5 suppression in endothelial cells (EC) on vascular endothelial growth factor (VEGF) and VEGFR-2 expression. αv was suppressed by shRNA in HUVEC (venous endothelial cells) and HMVEC (microvascular endothelial cells).VEGFR-2 was significantly upregulated by αv suppression in HUVEC and downregulated in HMVEC at both mRNA and protein levels,as assessed by real-time PCR and flow cytometry,respectively.HMVEC displayed completely abolished Sp1 binding to the VEGFR-2 promoter, and HUVEC exhibited enhanced binding to the –170 E- Box element in the VEGFR-2 promoter, assessed by electrophoretic mobility shift assay. Realtime PCR also revealed opposite effects on the expression of 5 additional important genes involved in angiogenesis in the two cell types.VEGF mRNA expression was enhanced in HUVEC and reduced in HMVEC; however, these alterations were not statistically significant.VEGF-induced proliferation was upregulated in HUVEC and reduced in HMVEC following αv suppression. No tube formation on Matrigel was observed in αv suppressed cells, regardless of their origin.These results indicate that suppression of αv integrins can either augment or inhibit VEGFR-2 levels and VEGF-induced proliferation in EC from different vascular beds. Hence, therapeutic antiangiogenic intervention by siRN-Amediated suppression of αv integrins should take into account variable and potentially hazardous responses in different vascular beds.

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Soudais, Claire, Sylvie Boutin, Saw See Hong, Miguel Chillon, Olivier Danos, Jeffrey M. Bergelson, Pierre Boulanger, and Eric J. Kremer. "Canine Adenovirus Type 2 Attachment and Internalization: Coxsackievirus-Adenovirus Receptor, Alternative Receptors, and an RGD-Independent Pathway." Journal of Virology 74, no. 22 (November 15, 2000): 10639–49. http://dx.doi.org/10.1128/jvi.74.22.10639-10649.2000.

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ABSTRACT The best-characterized receptors for adenoviruses (Ads) are the coxsackievirus-Ad receptor (CAR) and integrins αvβ5 and αvβ3, which facilitate entry. The αv integrins recognize an Arg-Gly-Asp (RGD) motif found in some extracellular matrix proteins and in the penton base in most human Ads. Using a canine adenovirus type 2 (CAV-2) vector, we found that CHO cells that express CAR but not wild-type CHO cells are susceptible to CAV-2 transduction. Cells expressing αMβ2 integrins or major histocompatibility complex class I (MHC-I) molecules but which do not express CAR were not transduced. Binding assays showed that CAV-2 attaches to a recombinant soluble form of CAR and that Ad type 5 (Ad5) fiber, penton base, and an anti-CAR antibody partially blocked attachment. Using fluorescently labeled CAV-2 particles, we found that in some cells nonpermissive for transduction, inhibition was at the point of internalization and not attachment. The transduction efficiency of CAV-2, which lacks an RGD motif, surprisingly mimicked that of Ad5 when tested in cells selectively expressing αvβ5 and αvβ3integrins. Our results demonstrate that CAV-2 transduction is augmented by CAR and possibly by αvβ5, though transduction can be CAR and αvβ3/5independent but is αMβ2, MHC-I, and RGD independent, demonstrating a transduction mechanism which is distinct from that of Ad2/5.

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Capasso, Domenica, Annarita Del Gatto, Daniela Comegna, Luigi Russo, Roberto Fattorusso, Michele Saviano, Sonia Di Gaetano, and Laura Zaccaro. "Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide." Molecules 25, no. 18 (September 19, 2020): 4298. http://dx.doi.org/10.3390/molecules25184298.

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Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma.

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Gladson, C. L., J. N. Wilcox, G. Y. Gillespie, and D. A. Cheresh. "DISTINCT GLIOBLASTOMA CELL LOCALIZATION OF INTEGRINS αvβ3 AND αvβ5." Journal of Neuropathology and Experimental Neurology 52, no. 3 (May 1993): 266. http://dx.doi.org/10.1097/00005072-199305000-00026.

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Yokosaki, Yasuyuki, Kumi Tanaka, Fumiko Higashikawa, Keisuke Yamashita, and Akira Eboshida. "Distinct structural requirements for binding of the integrins αvβ6, αvβ3, αvβ5, α5β1 and α9β1 to osteopontin." Matrix Biology 24, no. 6 (September 2005): 418–27. http://dx.doi.org/10.1016/j.matbio.2005.05.005.

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Jackson, Terry, Stuart Clark, Stephen Berryman, Alison Burman, Stephanie Cambier, Dezhi Mu, Stephen Nishimura, and Andrew M. Q. King. "Integrin αvβ8 Functions as a Receptor for Foot-and-Mouth Disease Virus: Role of the β-Chain Cytodomain in Integrin-Mediated Infection." Journal of Virology 78, no. 9 (May 1, 2004): 4533–40. http://dx.doi.org/10.1128/jvi.78.9.4533-4540.2004.

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ABSTRACT Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use three αv integrins, αvβ1, αvβ3, and αvβ6, as cellular receptors. Binding to the integrin is mediated by a highly conserved RGD motif located on a surface-exposed loop of VP1. The RGD tripeptide is recognized by several other members of the integrin family, which therefore have the potential to act as receptors for FMDV. Here we show that SW480 cells are made susceptible to FMDV following transfection with human β8 cDNA and expression of αvβ8 at the cell surface. The involvement of αvβ8 in infection was confirmed by showing that virus binding and infection of the transfected cells are inhibited by RGD-containing peptides and by function-blocking monoclonal antibodies specific for either the αvβ8 heterodimer or the αv chain. Similar results were obtained with a chimeric αvβ8 including the β6 cytodomain (αvβ8/6), showing that the β6 cytodomain can substitute efficiently for the corresponding region of β8. In contrast, virus binding to αvβ6 including the β8 cytodomain (αvβ6/8) was lower than that of the wild-type integrin, and this binding did not lead to infection. Further, the αvβ6 chimera was recognized poorly by antibodies specific for the ectodomain of αvβ6 and displayed a relaxed sequence-binding specificity relative to that of wild-type integrin. These data suggest that the β6 cytodomain is important for maintaining αvβ6 in a conformation required for productive infection by FMDV.

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Nandrot, Emeline F., Monika Anand, Mousumi Sircar, and Silvia C. Finnemann. "Novel role for αvβ5-integrin in retinal adhesion and its diurnal peak." American Journal of Physiology-Cell Physiology 290, no. 4 (April 2006): C1256—C1262. http://dx.doi.org/10.1152/ajpcell.00480.2005.

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αvβ5-Integrin is the sole integrin receptor at the retinal pigment epithelium (RPE)-photoreceptor interface and promotes RPE phagocytic signaling to the tyrosine kinase Mer tyrosine kinase (MerTK) once a day in response to circadian photoreceptor shedding. Herein we identify a novel role for αvβ5-integrin in permanent RPE-photoreceptor adhesion that is independent of αvβ5's function in retinal phagocytosis. To compare retinal adhesion of wild-type and β 5 -integrin −/− mice, we mechanically separated RPE and neural retina and quantified RPE protein and pigment retention with the neural retina. Lack of αvβ5-integrin with normal expression of other RPE integrins greatly weakened retinal adhesion in young mice and accelerated its age-dependent decline. Unexpectedly, the strength of wild-type retinal adhesion varied with a diurnal rhythm that peaked 3.5 h after light onset, after the completion of phagocytosis, when integrin signaling to MerTK is minimal. Permanent αvβ5 receptor deficiency attenuated the diurnal peak of retinal adhesion in β 5 -integrin −/− mice. These results identify αvβ5-integrin as the first RPE receptor that contributes to retinal adhesion, a vital mechanism for long-term photoreceptor function and viability. Furthermore, they indicate that αvβ5 receptors at the same apical plasma membrane domain of RPE cells fulfill two separate functions that are synchronized by different diurnal rhythms.

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Beauvais, DeannaLee M., Brian J. Ell, Andrea R. McWhorter, and Alan C. Rapraeger. "Syndecan-1 regulates αvβ3 and αvβ5 integrin activation during angiogenesis and is blocked by synstatin, a novel peptide inhibitor." Journal of Experimental Medicine 206, no. 3 (March 2, 2009): 691–705. http://dx.doi.org/10.1084/jem.20081278.

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Syndecan-1 (Sdc1) is a matrix receptor shown to associate via its extracellular domain with the αvβ3 and αvβ5 integrins, potentially regulating cell adhesion, spreading, and invasion of cells expressing these integrins. Using Sdc1 deletion mutants expressed in human mammary carcinoma cells, we identified the active site within the Sdc1 core protein and derived a peptide inhibitor called synstatin (SSTN) that disrupts Sdc1's interaction with these integrins. Because the αvβ3 and αvβ5 integrins are critical in angiogenesis, a process in which a role for Sdc1 has been uncertain, we used human vascular endothelial cells in vitro to show that the Sdc1 regulatory mechanism is also required for integrin activation on these cells. We found Sdc1 expressed in the vascular endothelium during microvessel outgrowth from aortic explants in vitro and in mouse mammary tumors in vivo. Moreover, we show that SSTN blocks angiogenesis in vitro or when delivered systemically in a mouse model of angiogenesis in vivo, and impairs mammary tumor growth in an orthotopic mouse tumor model. Thus, Sdc1 is a critical regulator of these two important integrins during angiogenesis and tumorigenesis, and is inhibited by the novel SSTN peptide.

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Weller, Michael, Manuela Silginer, Simon L. Goodman, Kathy Hasenbach, Svenja Thies, Peter Schraml, Ghazaleh Tabatabai, Holger Moch, Isabel Tritschler, and Patrick Roth. "Effect of the integrin inhibitor cilengitide on TGF-beta signaling." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 2055. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.2055.

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2055 Background: Glioblastoma is the most malignant form of intrinsic brain tumors. One of its characteristic features, angiogenesis, is mediated by the expression of integrins αvβ3 and αvβ5 on tumor-associated vasculature. Cilengitide is a synthetic peptide which inhibits ligand binding to the αvβ3 and αvβ5 integrins. The addition of cilengitide to the standard treatment regimen of radiochemotherapy in patients with newly diagnosed glioblastoma demonstrated promising results without significant toxicity which led to the initiation of a randomized phase registration III trial. Besides other functions, av-integrins can be involved in the activation of the cytokine transforming growth factor (TGF)-β which contributes to the malignant phenotype of glioma cells. Methods: Integrin expression was examined by immunohistochemistry and flow cytometry. The effects of cilengitide on TGF-β signaling in glioma cells were investigated by PCR, immunoblot and ELISA. Further assessments included reporter assays and glioma xenografts in nude mice. Results: The target integrins of cilengitide are expressed in glioblastoma blood vessels and tumor cells. Exposure to cilengitide results in detachment and reduced phosphorylation of Smad2 in most glioma cell lines, including stem-like glioma cells. Furthermore, exposure of glioma cells to cilengitide is associated with reduced TGF-β-mediated reporter gene activity. Smad2 phosphorylation, but not attachment, can be rescued by co-exposure to recombinant TGF-β. Cilengitide results in decreased TGF-β1 and TGF-β2 mRNA and protein expression and loss of transcriptional activity of the TGF-β promoter. Blocking antibodies to integrins αv, αvβ3 or αvβ5, or silencing of integrins αv, β3, β5 or β8 by RNA interference mimics the effects of cilengitide on TGF-β expression. Intracranial LN-308 glioma xenografts in nude mice display reduced pSmad2 levels in response to cilengitide. Conclusions: This study demonstrate a novel mechanism which may in part mediate anti-glioblastoma activity of cilengitide. These anti-TGF-β properties of cilengitide might be exploited in future clinical trials.

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Cafaro, Aurelio, Giovanni Barillari, Sonia Moretti, Clelia Palladino, Antonella Tripiciano, Mario Falchi, Orietta Picconi, et al. "HIV-1 Tat Protein Enters Dysfunctional Endothelial Cells via Integrins and Renders Them Permissive to Virus Replication." International Journal of Molecular Sciences 22, no. 1 (December 30, 2020): 317. http://dx.doi.org/10.3390/ijms22010317.

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Previous work has shown that the Tat protein of Human Immunodeficiency Virus (HIV)-1 is released by acutely infected cells in a biologically active form and enters dendritic cells upon the binding of its arginine-glycine-aspartic acid (RGD) domain to the α5β1, αvβ3, and αvβ5 integrins. The up-regulation/activation of these integrins occurs in endothelial cells exposed to inflammatory cytokines that are increased in HIV-infected individuals, leading to endothelial cell dysfunction. Here, we show that inflammatory cytokine-activated endothelial cells selectively bind and rapidly take up nano-micromolar concentrations of Tat, as determined by flow cytometry. Protein oxidation and low temperatures reduce Tat entry, suggesting a conformation- and energy-dependent process. Consistently, Tat entry is competed out by RGD-Tat peptides or integrin natural ligands, and it is blocked by anti-α5β1, -αvβ3, and -αvβ5 antibodies. Moreover, modelling–docking calculations identify a low-energy Tat-αvβ3 integrin complex in which Tat makes contacts with both the αv and β3 chains. It is noteworthy that internalized Tat induces HIV replication in inflammatory cytokine-treated, but not untreated, endothelial cells. Thus, endothelial cell dysfunction driven by inflammatory cytokines renders the vascular system a target of Tat, which makes endothelial cells permissive to HIV replication, adding a further layer of complexity to functionally cure and/or eradicate HIV infection.

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Bureyko, T., H. Hurdle, J. B. Metcalfe, M. T. Clandinin, and Vera C. Mazurak. "Reduced growth and integrin expression of prostate cells cultured with lycopene, vitamin E and fish oil in vitro." British Journal of Nutrition 101, no. 7 (August 21, 2008): 990–97. http://dx.doi.org/10.1017/s0007114508051684.

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Integrins are transmembrane proteins that facilitate the interaction of cells with the extracellular environment. They have also been implicated in cancer progression. The effects of nutrients thought to be involved in the prevention of prostate cancer on integrin expression have not been determined. Prostate cancer cell lines representing a range of malignancy from normal (RWPE-1) to highly invasive phenotypes (22Rv1 < LNCaP < PC-3) were cultured with or without lycopene (10 nm), vitamin E (5 μm) or fish oil (100 μm) for 48 h. Growth and integrin (α2β1, αvβ3 and αvβ5) expression were assessed using Trypan Blue exclusion and monoclonal antibodies combined with flow cytometry. Vitamin E enhanced (P < 0·001) whereas fish oil reduced the growth of all the cell lines tested (P < 0·001). Lycopene had no effect on growth. All the malignant cell lines exhibited lower expression of α2β1 with the addition of lycopene to culture media. Supplemental fish oil reduced α2β1 in most invasive cell lines (LNCaP and PC-3). Each nutrient at physiological levels reduced integrins αvβ3 and αvβ5 in most invasive cell lines (PC-3). The results suggest that integrins may represent an additional target of bioactive nutrients and that the effects of nutrients may be dependent on the type of cell line used.

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Belvisi, Laura, Teresa Riccioni, Marcella Marcellini, Loredana Vesci, Ilaria Chiarucci, Daniela Efrati, Donatella Potenza, et al. "Biological and molecular properties of a new αvβ3/αvβ5 integrin antagonist." Molecular Cancer Therapeutics 4, no. 11 (November 2005): 1670–80. http://dx.doi.org/10.1158/1535-7163.mct-05-0120.

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Wickham, Thomas J., Patricia Mathias, David A. Cheresh, and Glen R. Nemerow. "Integrins αvβ3 and αvβ5 promote adenovirus internalization but not virus attachment." Cell 73, no. 2 (April 1993): 309–19. http://dx.doi.org/10.1016/0092-8674(93)90231-e.

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Zhang, Hongquan, Zhilun Li, Eva-Karin Viklund, and Staffan Strömblad. "p21-activated kinase 4 interacts with integrin αvβ5 and regulates αvβ5-mediated cell migration." Journal of Cell Biology 158, no. 7 (September 23, 2002): 1287–97. http://dx.doi.org/10.1083/jcb.200207008.

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p21-activated kinase 1 (PAK1) can affect cell migration (Price et al., 1998; del Pozo et al., 2000) and modulate myosin light chain kinase and LIM kinase, which are components of the cellular motility machinery (Edwards, D.C., L.C. Sanders, G.M. Bokoch, and G.N. Gill. 1999. Nature Cell Biol. 1:253–259; Sanders, L.C., F. Matsumura, G.M. Bokoch, and P. de Lanerolle. 1999. Science. 283:2083–2085). We here present a novel cell motility pathway by demonstrating that PAK4 directly interacts with an integrin intracellular domain and regulates carcinoma cell motility in an integrin-specific manner. Yeast two-hybrid screening identified PAK4 binding to the cytoplasmic domain of the integrin β5 subunit, an association that was also found in mammalian cells between endogenous PAK4 and integrin αvβ5. Furthermore, we mapped the PAK4 binding to the membrane-proximal region of integrin β5, and identified an integrin-binding domain at aa 505–530 in the COOH terminus of PAK4. Importantly, engagement of integrin αvβ5 by cell attachment to vitronectin led to a redistribution of PAK4 from the cytosol to dynamic lamellipodial structures where PAK4 colocalized with integrin αvβ5. Functionally, PAK4 induced integrin αvβ5–mediated, but not β1-mediated, human breast carcinoma cell migration, while no changes in integrin cell surface expression levels were observed. In conclusion, our results demonstrate that PAK4 interacts with integrin αvβ5 and selectively promotes integrin αvβ5–mediated cell migration.

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Crockett, Julie C., Norbert Schütze, Denise Tosh, Susanne Jatzke, Angela Duthie, Franz Jakob, and Michael J. Rogers. "The Matricellular Protein CYR61 Inhibits Osteoclastogenesis by a Mechanism Independent of αvβ3 and αvβ5." Endocrinology 148, no. 12 (December 1, 2007): 5761–68. http://dx.doi.org/10.1210/en.2007-0473.

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Cysteine-rich protein 61 (CYR61/CCN1) belongs to the family of CCN matricellular proteins. Most of the known effects of CCN proteins appear to be due to binding to extracellular growth factors or integrins, including αvβ3 and αvβ5. Although CYR61 can stimulate osteoblast differentiation, until now the effect of CYR61 on osteoclasts was unknown. We demonstrate that recombinant human CYR61 inhibits the formation of multinucleated, αvβ3-positive, or tartrate-resistant acid phosphatase-positive human, mouse, and rabbit osteoclasts in vitro. CYR61 markedly reduced the expression of the osteoclast phenotypic markers tartrate-resistant acid phosphatase, matrix metalloproteinase-9, calcitonin receptor, and cathepsin K. However, CYR61 did not affect the formation of multinucleated osteoclasts when added to osteoclast precursors prior to fusion or affect the number or resorptive activity of osteoclasts cultured on dentine discs, indicating that CYR61 affects early osteoclast precursors but not mature osteoclasts. CYR61 did not affect receptor activator of nuclear factor-κB (RANK) ligand-induced phosphorylation of p38 or ERK1/2 in human macrophages and did not affect RANK ligand-induced activation of nuclear factor-κB, indicating that CYR61 does not appear to inhibit osteoclastogenesis by affecting RANK signaling. Furthermore, a mutant form of CYR61 defective in binding to αvβ3 also inhibited osteoclastogenesis, and CYR61 inhibited osteoclastogenesis similarly in cultures of mouse wild-type or β5−/− macrophages. Thus, CYR61 does not appear to inhibit osteoclast formation by interacting with αvβ3 or αvβ5. These observations demonstrate that CYR61 is a hitherto unrecognized inhibitor of osteoclast formation, although the exact mechanism of inhibition remains to be determined. Given that CYR61 also stimulates osteoblasts, CYR61 could represent an important bifunctional local regulator of bone remodeling.

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Eliceiri, Brian P., Xose S. Puente, John D. Hood, Dwayne G. Stupack, David D. Schlaepfer, Xiaozhu Z. Huang, Dean Sheppard, and David A. Cheresh. "Src-mediated coupling of focal adhesion kinase to integrin αvβ5 in vascular endothelial growth factor signaling." Journal of Cell Biology 157, no. 1 (April 1, 2002): 149–60. http://dx.doi.org/10.1083/jcb.200109079.

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Vascular endothelial growth factor (VEGF) promotes vascular permeability (VP) and neovascularization, and is required for development. We find that VEGF-stimulated Src activity in chick embryo blood vessels induces the coupling of focal adhesion kinase (FAK) to integrin αvβ5, a critical event in VEGF-mediated signaling and biological responsiveness. In contrast, FAK is constitutively associated with β1 and β3 integrins in the presence or absence of growth factors. In cultured endothelial cells, VEGF, but not basic fibroblast growth factor, promotes the Src-mediated phosphorylation of FAK on tyrosine 861, which contributes to the formation of a FAK/αvβ5 signaling complex. Moreover, formation of this FAK/αvβ5 complex is significantly reduced in pp60c-src-deficient mice. Supporting these results, mice deficient in either pp60c-src or integrin β5, but not integrin β3, have a reduced VP response to VEGF. This FAK/αvβ5 complex was also detected in epidermal growth factor-stimulated epithelial cells, suggesting a function for this complex outside the endothelium. Our findings indicate that Src can coordinate specific growth factor and extracellular matrix inputs by recruiting integrin αvβ5 into a FAK-containing signaling complex during growth factor–mediated biological responses.

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Wang, Weijun, Nian-Ling Zhu, Jason Chua, Steve Swenson, Fritz K. Costa, Stephanie Schmitmeier, Barbara A. Sosnowski, Toshiaki Shichinohe, Noriyuki Kasahara, and Thomas C. Chen. "Retargeting of adenoviral vector using basic fibroblast growth factor ligand for malignant glioma gene therapy." Journal of Neurosurgery 103, no. 6 (December 2005): 1058–66. http://dx.doi.org/10.3171/jns.2005.103.6.1058.

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Object. Adenovirus vector (AdV)—mediated gene delivery has been recently demonstrated in clinical trials as a novel potential treatment for malignant gliomas. Combined coxsackievirus B and adenovirus receptor (CAR) has been shown to function as an attachment receptor for multiple adenovirus serotypes, whereas the vitronectin integrins (αvβ3 and αvβ5) are involved in AdV internalization. In resected glioma specimens, the authors demonstrated that malignant gliomas have varying levels of CAR, αvβ3, and αvβ5 expression. Methods. A correlation between CAR expression and the transduction efficiency of AdV carrying the green fluorescent protein in various human glioblastoma multiforme (GBM) cell lines and GBM primary cell lines was observed. To increase transgene activity in in vitro glioma cells with low or deficient levels of CAR, the authors used basic fibroblast growth factor (FGF2) as a targeting ligand to redirect adenoviral infection through its cognate receptor, FGF receptor 1 (FGFR1), which was expressed at high levels by all glioma cells. These findings were confirmed by in vivo study data demonstrating enhanced transduction efficiency of FGF2-retargeted AdV in CAR-negative intracranial gliomas compared with AdV alone, without evidence of increased angiogenesis. Conclusions. Altogether, the results demonstrated that AdV-mediated gene transfer using the FGF2/FGFR system is effective in gliomas with low or deficient levels of CAR and suggested that FGF2-retargeting of AdV may be a promising approach in glioma gene therapy.

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Xu, Jingying, Melissa Millard, Xiuhai Ren, Orla T. Cox, and Anat Erdreich-Epstein. "c-Abl mediates endothelial apoptosis induced by inhibition of integrins αvβ3 and αvβ5 and by disruption of actin." Blood 115, no. 13 (April 1, 2010): 2709–18. http://dx.doi.org/10.1182/blood-2009-05-223776.

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Abstract Inhibition of integrins αvβ3 and αvβ5 in human brain microvascular endothelial cells (HBMECs) by the function-blocking peptide RGDfV induces loss of spreading on vitronectin, cell detachment, and apoptosis. We demonstrate that cell detachment is not required for apoptosis because plating on bovine serum albumin–blocked poly-L-lysine (allows attachment, but not integrin ligation and cell spreading) also induced apoptosis. Latrunculin B (LatB), which inhibits F-actin polymerization, induced transient loss of HBMEC spreading on vitronectin, but not their detachment, and induced apoptosis despite recovery of cell spreading. However, LatB did not cause apoptosis in 5 tumor cell lines. In HBMECs, both LatB and RGDfV induced transient Y412 and Y245 phosphorylation of endogenous c-Abl, a nonreceptor tyrosine kinase that reciprocally regulates F-actin. LatB also induced nuclear translocation of c-Abl in HBMECs. STI-571 (imatinib), a targeted therapy for BCR-ABL1+ leukemias and inhibitor of c-Abl, platelet-derived growth factor receptor, and c-Kit, decreased endothelial apoptosis. LatB-induced HBMEC apoptosis, and its inhibition by STI-571 also occurred in a 3-dimensional collagen model, supporting physiologic relevance. Last, siRNA to c-Abl (but not nonspecific siRNA) also inhibited RGDfV- and LatB-induced apoptosis. Thus, endogenous c-Abl mediates endothelial apoptosis induced by inhibition of integrins αvβ3/αvβ5 or by LatB-induced disruption of F-actin.

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Retta, Saverio Francesco, Georgia Cassarà, Monica D'Amato, Riccardo Alessandro, Maurizio Pellegrino, Simona Degani, Giacomo De Leo, Lorenzo Silengo, and Guido Tarone. "Cross Talk between β1 and αVIntegrins: β1 Affects β3 mRNA Stability." Molecular Biology of the Cell 12, no. 10 (October 2001): 3126–38. http://dx.doi.org/10.1091/mbc.12.10.3126.

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There is increasing evidence that a fine-tuned integrin cross talk can generate a high degree of specificity in cell adhesion, suggesting that spatially and temporally coordinated expression and activation of integrins are more important for regulated cell adhesive functions than the intrinsic specificity of individual receptors. However, little is known concerning the molecular mechanisms of integrin cross talk. With the use of β1-null GD25 cells ectopically expressing the β1A integrin subunit, we provide evidence for the existence of a cross talk between β1 and αVintegrins that affects the ratio of αVβ3 and αVβ5integrin cell surface levels. In particular, we demonstrate that a down-regulation of αVβ3 and an up-regulation of αVβ5 occur as a consequence of β1A expression. Moreover, with the use of GD25 cells expressing the integrin isoforms β1B and β1D, as well as two β1 cytoplasmic domain deletion mutants lacking either the entire cytoplasmic domain (β1TR) or only its “variable” region (β1COM), we show that the effects of β1over αV integrins take place irrespective of the type of β1 isoform, but require the presence of the “common” region of the β1 cytoplasmic domain. In an attempt to establish the regulatory mechanism(s) whereby β1 integrins exert theirtrans-acting functions, we have found that the down-regulation of αVβ3 is due to a decreased β3 subunit mRNA stability, whereas the up-regulation of αVβ5 is mainly due to translational or posttranslational events. These findings provide the first evidence for an integrin cross talk based on the regulation of mRNA stability.

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Deroyer, C., E. Charlier, S. Neuville, Z. Plener, O. Malaise, F. Ciregia, P. Gillet, et al. "Towar a diagnostic relevance of αvβ5, αvβ3 and αvβ6 integrins in osteoarthritis. Expression within human cartilage and spinal osteophytes." Osteoarthritis and Cartilage 28 (April 2020): S205. http://dx.doi.org/10.1016/j.joca.2020.02.333.

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Škoberne, Mojca, Selin Somersan, Wanda Almodovar, Tuan Truong, Kseniya Petrova, Peter M. Henson, and Nina Bhardwaj. "The apoptotic-cell receptor CR3, but not αvβ5, is a regulator of human dendritic-cell immunostimulatory function." Blood 108, no. 3 (August 1, 2006): 947–55. http://dx.doi.org/10.1182/blood-2005-12-4812.

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Abstract Dendritic cells (DCs) that capture apoptotic cells (ACs) in the steady state mediate peripheral tolerance to self-antigens. ACs are recognized by an array of receptors on DCs, the redundancy of which is not completely defined. We made use of an AC surrogate system to address the individual roles of the αvβ5 and complement receptors (CRs) in the phagocytosis and induction of immunity. CR3 and CR4, while substantially less efficient than αvβ5 in internalizing ACs, initiate signals that render DCs tolerogenic. Responding T cells show impaired proliferation and IFNγ production and subsequently die by apoptosis. While tolerogenic DCs are not induced via αvβ5, coligation of CR3 and αvβ5 maintains the DC's tolerogenic profile. This immunomodulatory role, however, is countered by a significant inflammatory stimulus such as bacterial infection. Overall, our data suggest that under steady-state conditions, signaling via CRs predominates to render DCs tolerogenic.

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Zhang, Dan, Chichi Li, Yuanlin Song, Jian Zhou, Yuping Li, Jing Li, and Chunxue Bai. "Integrin αvβ5 inhibition protects against ischemia-reperfusion-induced lung injury in an autophagy-dependent manner." American Journal of Physiology-Lung Cellular and Molecular Physiology 313, no. 2 (August 1, 2017): L384—L394. http://dx.doi.org/10.1152/ajplung.00391.2016.

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Integrin αvβ5 mediates pulmonary endothelial barrier function and acute lung injury (LI), but its roles in cell apoptosis and autophagy are unclear. Thus, the aims of this study were to investigate the significance of αvβ5 in ischemia-reperfusion (I/R)-induced apoptosis and LI and to explore the relationship between αvβ5 and autophagy. Human pulmonary microvascular endothelial cells (HPMVECs) were pretreated with an αvβ5-blocking antibody (ALULA) and challenged with oxygen-glucose deprivation/oxygen-glucose restoration, which mimics I/R; then, cellular autophagy and apoptosis were detected, and cell permeability was assessed. In vivo, mice were pretreated with the autophagy inhibitor chloroquine (CLQ), followed by treatment with ALULA. The mice then underwent operative lung I/R. LI was assessed by performing a pathological examination, calculating the wet/dry lung weight ratio and detecting the bronchial alveolar lavage fluid (BALF) protein concentration. αvβ5 inhibition promoted HPMVEC autophagy under I/R in vitro, alleviated cell permeability, decreased the apoptosis ratio, and activated caspase-3 expression. These outcomes were significantly diminished when autophagy was inhibited with a small-interfering RNA construct targeting autophagy-related gene 7 (si ATG7). Moreover, ALULA pretreatment alleviated I/R-induced LI (I/R-LI), which manifested as a decreased wet/dry lung weight ratio, an altered BALF protein concentration, and lung edema. Preinhibiting autophagy with CLQ, however, eliminated the protective effects of ALULA on I/R-LI. Therefore, inhibiting αvβ5 effectively ameliorated I/R-induced endothelial cell apoptosis and I/R-LI. This process was dependent on improved autophagy and its inhibitory effects on activated caspase-3.

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Sinanan, Andrea C. M., Jon R. A. Machell, G. Trevor Wynne-Hughes, Nigel P. Hunt, and Mark P. Lewis. "αvβ3 and αvβ5 integrins and their role in muscle precursor cell adhesion." Biology of the Cell 100, no. 8 (August 2008): 465–77. http://dx.doi.org/10.1042/bc20070115.

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Bellahcène, A., M. Chaplet, K. Bonjean, and V. Castronovo. "Zoledronate Inhibits αvβ3 and αvβ5 Integrin Cell Surface Expression in Endothelial Cells." Endothelium 14, no. 2 (January 2007): 123–30. http://dx.doi.org/10.1080/10623320701347187.

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Sinanan, Andrea C. M., Jon R. A. Machell, G. Trevor Wynne-Hughes, Nigel P. Hunt, and Mark P. Lewis. "αvβ3 and αvβ5 integrins and their role in muscle precursor cell adhesion." Biology of the Cell 100, no. 12 (December 2008): 727. http://dx.doi.org/10.1111/j.1768-322x.2008.tb01436.x.

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Journal articles on the topic 'Αvβ5'

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