Integrin alpha-V beta-3, Integrin alpha-V beta-5, Integrin alpha-V beta-6 (αvβ3, αvβ5, αvβ6)

Integrins αvβ3, αvβ5, and αvβ6 are heterodimeric transmembrane cell surface receptors that belong to the integrin family, composed of α (alpha) and β (beta) subunits. These integrins primarily act as receptors for extracellular matrix proteins containing the RGD (Arg-Gly-Asp) motif, such as vitronectin, fibronectin, and osteopontin[1][4][6][7]. Structurally, the αvβ3 integrin consists of a seven-bladed β-propeller from the alpha subunit and an I-like domain from the beta subunit, forming a ligand-binding head and two "legs" composed of multiple domains, enabling it to mediate cell–matrix adhesion and bidirectional signaling across the plasma membrane[1][2][3]. Conformational changes are central to its activation and affinity regulation for ligands. Functionally, these integrins are involved in cell adhesion, migration, and proliferation, and are essential in physiological processes like angiogenesis (new blood vessel formation), wound healing, and immune responses[3][4][7]. Overexpression or dysregulation is implicated in pathologies including cancer (where they mediate tumor angiogenesis and metastasis), fibrosis, and chronic inflammation[3][6]. Therapeutically, these integrins are validated drug targets, with several antagonists (e.g., cilengitide) and monoclonal antibodies (e.g., etaracizumab, vitaxin) studied in cancer and other diseases for their ability to block pathological cell adhesion, migration, and angiogenesis[6]. Safety profiles are influenced by their role in physiological angiogenesis and thrombosis[5][7]. Variants (αvβ3, αvβ5, αvβ6) differ in tissue distribution and ligand specificity but share significant structural and functional homology. The presence of these integrins on tumor vasculature has made them biomarkers for anti-angiogenic therapy and targets for molecular imaging[3][6][7].

Other names

Integrin αvβ3: CD51/CD61Integrin αvβ3: vitronectin receptorIntegrin αvβ3: ITGAV/ITGB3Integrin αvβ5: CD51/CD65Integrin αvβ5: ITGAV/ITGB5Integrin αvβ6: CD51/CD103Integrin αvβ6: ITGAV/ITGB6

Inhibition of integrin-ligand binding (blocks RGD motif interaction) Anti-angiogenic effects (inhibit new blood vessel growth) Induction of apoptosis in target cells (e.g., caspase-8 recruitment by ProAgio) Inhibition of cell adhesion and migration