Vascular endothelial growth factor receptor-1 is deposited in the extracellular matrix by endothelial cells and is a ligand for the alpha 5 beta 1 integrin.

Vascular endothelial growth factor receptor-1 (VEGFR-1) is a tyrosine kinase receptor for several growth factors of the VEGF family. Endothelial cells express a membrane-spanning form of VEGFR-1 and secrete a soluble variant of the receptor comprising only the extracellular region. The role of this variant has not yet been completely defined. In this study, we report that the secreted VEGFR-1 is present within the extracellular matrix deposited by endothelial cells in culture, suggesting a possible involvement in endothelial cell adhesion and migration. In adhesion assays, VEGFR-1 extracellular region specifically promoted endothelial cell attachment. VEGFR-1-mediated cell adhesion was divalent cation-dependent, and inhibited by antibodies directed against the alpha 5 beta 1 integrin. Moreover, VEGFR-1 promoted endothelial cell migration, and this effect was inhibited by anti-alpha 5 beta 1 antibodies. Direct binding of VEGFR-1 to the alpha 5 beta 1 integrin was also detected. Finally, binding to VEGFR-1 initiated endothelial cell spreading. Altogether these results indicate that the soluble VEGFR-1 secreted by endothelial cells becomes a matrix-associated protein that is able to interact with the alpha 5 beta 1 integrin, suggesting a new role of VEGFR-1 in angiogenesis, in addition to growth factor binding.