Endothelial cell integrin receptor

Endothelial cell integrin receptors are a family of heterodimeric transmembrane proteins, consisting of alpha and beta subunits, that mediate the interaction between endothelial cells and the extracellular matrix (ECM) (Avraamides et al., 2008). These receptors, most notably alpha-v beta-3, alpha-v beta-5, and alpha-5 beta-1, are essential regulators of vascular biology, controlling processes such as cell survival, proliferation, and migration during angiogenesis (Desgrosellier & Cheresh, 2010). While their expression is low in stable, mature vessels, they are significantly upregulated in the neovasculature of tumors and at sites of chronic inflammation, making them attractive targets for therapeutic intervention (Ley et al., 2016). In the context of cancer, drugs targeting these integrins aim to inhibit the formation of new blood vessels that sustain tumor growth and facilitate metastasis. Various therapeutic agents, including the cyclic RGD peptide cilengitide and several monoclonal antibodies like etaracizumab, have been developed to block these receptors (Stupp et al., 2014). Despite strong preclinical evidence, many of these therapies have struggled in clinical trials, often failing to improve overall survival, which may be due to the functional redundancy of integrin signaling or paradoxical effects at certain drug concentrations (Reynolds et al., 2009). Beyond oncology, endothelial integrins are also being explored as biomarkers for imaging active angiogenesis and as targets in ocular and inflammatory diseases (Beer et al., 2006).

Other names

Integrin receptorVascular integrinEndothelial integrinAdhesion receptorIntegrin alpha-v beta-3Integrin alpha-v beta-5Integrin alpha-5 beta-1

Antagonism of the extracellular binding site for RGD (Arg-Gly-Asp) motifs found in extracellular matrix proteins, which prevents integrin activation and downstream signaling through focal adhesion kinase (FAK) and Src, thereby inhibiting endothelial cell survival, proliferation, and migration (Desgrosellier & Cheresh, 2010; Avraamides et al., 2008).