title: The synergistic activity of alphavbeta3 integrin and PDGF receptor increases cell migration.
abstract: Integrins and growth factor receptors act synergistically to modulate cellular functions. The alphavbeta3 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 alphavbeta3 and RGD-dependent manner. In contrast, this response was not observed on a beta1 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 (2.4- or 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 factor-BB stimulation of NIH-3T3 cells did not alter the ability of alphavbeta3 to bind RGD immobilized on Sepharose. The alphavbeta3 integrin and the platelet derived growth factor receptor-beta associate in both microvascular endothelial cells and NIH-3T3 cells, since they coprecipitated using two different antibodies to either alphavbeta3 or to the platelet derived growth factor receptor-beta. In contrast, beta1 integrins did not coprecipitate with the platelet derived growth factor receptor-beta. These results point to a novel pathway, mediated by the synergistic activity of alphavbeta3 and the platelet derived growth factor receptor-beta, that regulates cell migration and, therefore, might play a role during neovessel formation and tissue infiltration.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Woodard
authors.forename: G
authors.initials: G
authors.lastname: García-Cardeña
authors.forename: M
authors.initials: M
authors.lastname: Leong
authors.forename: J A
authors.initials: JA
authors.lastname: Madri
authors.forename: W C
authors.initials: WC
authors.lastname: Sessa
authors.forename: L R
authors.initials: LR
authors.lastname: Languino
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D000077214:Becaplermin; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D039564:Integrin alphaV; D007797:Laminin; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism / Q000502:physiology*; D019030:Receptors, Vitronectin / Q000302:isolation & purification / Q000378:metabolism*; D019096:Vitronectin
chemical_list: D015703:Antigens, CD; D039564:Integrin alphaV; D007797:Laminin; D009842:Oligopeptides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D019030:Receptors, Vitronectin; D019096:Vitronectin; D000077214:Becaplermin; C047981:arginyl-glycyl-aspartic acid; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor