Integrin alpha9beta1 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.15187-15196
• Main Authors: Vlahakis, Nicholas E, Young, Bradford A, Atakilit, Amha, Hawkridge, Anne E, Issaka, Rachel B, Boudreau, Nancy, Sheppard, Dean
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell Movement - drug effects; Cell Movement - physiology; Cells, Cultured; Endothelial Cells - metabolism; Fibroblasts - metabolism; Humans; Integrins - agonists; Integrins - metabolism; Mice; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Physiologic - drug effects; Protein Binding - drug effects; Protein Binding - physiology; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor C - metabolism; Vascular Endothelial Growth Factor C - pharmacology; Vascular Endothelial Growth Factor D - metabolism; Vascular Endothelial Growth Factor D - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 0021-9258

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 alpha9beta1 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 alpha9beta1 and the cognate receptor for VEGF-A, VEGF receptor 2 (VEGF-R2). Unlike alpha3beta1or alphavbeta3 integrins, alpha9beta1 was also found to bind the 121 isoform of VEGF-A. This interaction appears to be biologically significant, because alpha9beta1-blocking antibody dramatically and specifically inhibited angiogenesis induced by VEGF-A165 or -121. Together with our previous findings that alpha9beta1 directly binds to VEGF-C and -D and contributes to lymphangiogenesis, these results identify the integrin alpha9beta1 as a potential pharmacotherapeutic target for inhibition of pathogenic angiogenesis and lymphangiogenesis.