Integrin activation is required for VEGF and FGF receptor protein presenceon human microvascular endothelial cells

Endothelial cell proliferation and migration is initiated by growth factors including FGF and VEGF that bind to specific transmembrane receptor tyrosi ne kinases. Mechanisms that regulate in vivo expression of fibroblast growt h factor receptors (FGFR) and vascular endothelial growth factor receptors (VEGFR) are not well understood. Since it is well known that different matr ices influence the proliferation and migration of endothelial cells in cult ure, we hypothesized that changes in the extracellular matrix environment c an regulate growth factor receptors on endothelial cells. We cultured human microvascular endothelial cells on different matrices (vitronectin, lamini n, fibronectin, fibrin, and collagen IV) and examined for the presence of g rowth factor receptors (FGFR-1, FGFR-2, VEGFR-1, and VEGFR-2). We show that vitronectin increased the presence of all four growth factor receptors and most notably, VEGFR-1. In contrast, fibrin decreased all four receptors, e specially FGFR-1 and FGFR-2. Inhibiting phosphotyrosine signaling abolished immunostaining for all four receptors, regardless of the matrix, but was n ot dependent on activating the Fyn-Shc pathway. Cells plated on vitronectin in the presence of blocking antibodies to integrins alpha (v)beta (3) and alpha (v)beta (5) similarly decreased presence of these growth factor recep tors. Our data suggests a possible mechanism of how matrix-integrin interac tions regulate endothelial cell responsiveness to growth factors and anchor age-dependent cell growth.