The synergistic activity of alphavbeta3 integrin and PDGF receptor increases cell migration

J Cell Sci. 1998 Feb:111 ( Pt 4):469-78. doi: 10.1242/jcs.111.4.469.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Antigens, CD / analysis
  • Becaplermin
  • Cell Adhesion
  • Cell Division
  • Cell Movement / physiology*
  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Humans
  • Integrin alphaV
  • Laminin
  • Mice
  • Oligopeptides / metabolism
  • Platelet-Derived Growth Factor / pharmacology
  • Proto-Oncogene Proteins c-sis
  • Rats
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Receptors, Platelet-Derived Growth Factor / physiology*
  • Receptors, Vitronectin / isolation & purification
  • Receptors, Vitronectin / metabolism*
  • Vitronectin

Substances

  • Antigens, CD
  • Integrin alphaV
  • Laminin
  • Oligopeptides
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Receptors, Vitronectin
  • Vitronectin
  • Becaplermin
  • arginyl-glycyl-aspartic acid
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor