The synergistic activity of αvβ3 integrin and PDGF receptor increases cell migration

Integrins and growth factor receptors act synergistically to modulate cellular functions. The αvβ3 integrin and the platelet-derived growth factor receptor have both been shown to play a positive role in cell migration. We show here that a platelet derived growth factor-BB gradient stimulated migration of rat microvascular endothelial cells on vitronectin (9.2-fold increase compared to resting cells) in a αvβ3 and RGD-dependent manner. In contrast, this response was not observed on a β1 integrin ligand, laminin; background levels of migration, in response to a platelet derived growth factor-BB gradient, were observed on this substrate or on bovine serum albumin (2.4or 2.0-fold, respectively). Comparable results were obtained using NIH-3T3 cells. Platelet derived growth factor-BB did not change the cells’ ability to adhere to vitronectin, nor did it stimulate a further increase in proliferation on vitronectin versus laminin. In addition, platelet derived growth factorBB stimulation of NIH-3T3 cells did not alter the ability of αvβ3 to bind RGD immobilized on Sepharose. The αvβ3 integrin and the platelet derived growth factor receptor-β associate in both microvascular endothelial cells and NIH3T3 cells, since they coprecipitated using two different antibodies to either αvβ3 or to the platelet derived growth factor receptor-β. In contrast, β1 integrins did not coprecipitate with the platelet derived growth factor receptor-β. These results point to a novel pathway, mediated by the synergistic activity of αvβ3 and the platelet derived growth factor receptor-β, that regulates cell migration and, therefore, might play a role during neovessel formation and tissue infiltration.