Integrin alpha-V beta-3 (αvβ3) (αvβ3)

Integrin alpha-V beta-3 (αvβ3) is a heterodimeric transmembrane receptor composed of the αv (CD51) and β3 (CD61) subunits, belonging to the integrin family of cell adhesion molecules (UniProt P06756, P05106). It primarily recognizes the RGD (Arg-Gly-Asp) tripeptide motif found in extracellular matrix (ECM) proteins like vitronectin, fibronectin, and osteopontin, mediating critical cell-matrix and cell-cell interactions (PubMed: 26933730). In the context of the tumor microenvironment, αvβ3 is significantly upregulated on cancer-associated fibroblasts (CAFs), where it drives fibroblast activation, myofibroblast differentiation, and ECM stiffening (PubMed: 31064757). This activation facilitates tumor progression by promoting epithelial-mesenchymal transition (EMT), metabolic reprogramming, and the creation of a physical barrier against immune infiltration (PubMed: 28651511). Beyond CAFs, αvβ3 is a hallmark of angiogenic vascular endothelial cells and various aggressive tumor types, making it a versatile target for both therapy and molecular imaging. Clinical development has focused on RGD-mimetic inhibitors, such as cilengitide, and monoclonal antibodies to disrupt these pro-tumorigenic signals, though challenges remain in achieving robust clinical efficacy as a monotherapy (PubMed: 24583790).

Other names

Vitronectin receptorCD51/CD61ITGAV/ITGB3Integrin αvβ3Antigen CD51/CD61

Competitive inhibition of RGD-motif binding to the αvβ3 heterodimer, preventing downstream activation of FAK, Src, and Akt signaling pathways involved in cell survival, migration, and myofibroblast activation.