Integrin α9β1 directly binds to vascular endothelial growth factor (VEGF)-A and contributes to VEGF-A-induced angiogenesis

Abstract

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 α3β1 or 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. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.