Integrin α9β1 Directly Binds to Vascular Endothelial Growth Factor (VEGF)-A and Contributes to VEGF-A-induced Angiogenesis

• Published in: The Journal of biological chemistry 2007-05, Vol.282 (20), p.15187
• Main Authors: Nicholas E. Vlahakis, Bradford A. Young, Amha Atakilit, Anne E. Hawkridge, Rachel B. Issaka, Nancy Boudreau, Dean Sheppard
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M609323200

Vascular endothelial growth factor A (VEGF-A) is a potent inducer of angiogenesis. We now show that VEGF-A-induced adhesion and migration of human endothelial cells are dependent on the integrin α9β1 and that VEGF-A is a direct ligand for this integrin. Adhesion and migration of these cells on the 165 and 121 isoforms of VEGF-A depend on cooperative input from α9β1 and the cognate receptor for VEGF-A, VEGF receptor 2 (VEGF-R2). Unlike α3β1or αvβ3 integrins, α9β1 was also found to bind the 121 isoform of VEGF-A. This interaction appears to be biologically significant, because α9β1-blocking antibody dramatically and specifically inhibited angiogenesis induced by VEGF-A165 or -121. Together with our previous findings that α9β1 directly binds to VEGF-C and -D and contributes to lymphangiogenesis, these results identify the integrin α9β1 as a potential pharmacotherapeutic target for inhibition of pathogenic angiogenesis and lymphangiogenesis.