CD47–integrin alpha-V beta-3 complex (CD47–αvβ3 complex)

The CD47–integrin alpha-V beta-3 complex is a functional signaling unit formed by the physical association of CD47 (Integrin-Associated Protein, IAP) and the heterodimeric integrin alpha-V beta-3 (αvβ3) (PMID: 8621498). This complex is crucial for modulating cell adhesion, migration, and calcium signaling, particularly in vascular cells and leukocytes (PMID: 10449401). In oncology, the CD47–αvβ3 interaction promotes tumor cell invasion, metastasis, and angiogenesis by enhancing integrin-mediated signaling pathways (PMID: 24658274). While CD47 is widely recognized for its 'don't eat me' signal via SIRPα, its association with αvβ3 specifically regulates the affinity of the integrin for extracellular matrix ligands like vitronectin (UniProt Q08722, P06756, P05106). Therapeutic targeting of this complex involves monoclonal antibodies such as Magrolimab or integrin inhibitors like Cilengitide to disrupt these pro-survival and pro-migratory signals (ClinicalTrials.gov). Disruption of this complex can lead to increased phagocytosis of tumor cells and decreased vascularization of the tumor microenvironment. However, challenges remain due to the ubiquitous expression of CD47 on healthy red blood cells, leading to potential hematologic toxicities like anemia. Research continues to explore bispecific antibodies or peptides that specifically target the interface of the CD47–αvβ3 complex to minimize off-target effects.

Other names

Integrin-associated protein–integrin alpha-V beta-3 complexIAP–αvβ3 complexCD47–vitronectin receptor complexCD47–ITGAV/ITGB3 complexCD47–integrin αvβ3 complex

The mechanisms of action for drugs targeting this complex include: 1) Blockade of the CD47-SIRPα 'don't eat me' signal to enhance macrophage-mediated phagocytosis (PMID: 19324461); 2) Inhibition of CD47-mediated 'inside-out' signaling that increases the affinity of integrin alpha-V beta-3 for its ligands (PMID: 9106657); 3) Disruption of integrin-mediated cell adhesion and migration to prevent metastasis (PMID: 22431538); and 4) Suppression of tumor-associated angiogenesis by interfering with vascular endothelial cell signaling (PMID: 24658274).