α5 and α2 integrin gene transfers mimic the PDGF-B-induced transformed phenotype of fibroblasts in human skin

Abstract

Platelet-derived growth factor (PDGF)-B is a proto-oncogene capable of transforming fibroblasts. Using adenoviral vectors, we tested whether endogenous PDGF-B expression in human skin xenotransplants leads to changes in the expression of α5 and α2 integrin subunits and whether integrin overexpression leads to PDGF-related changes in the skin. In vitro, transduction of fibroblasts with PDGF-B or the integrin α5 subunit stimulated multilayered growth and spindle-type morphology, both markers of mesenchymal cell transformation. In vivo, PDGF-B transduction of the human dermis was associated with up-regulation of collagen and fibronectin synthesis, increases in α5 and α2 integrin subunit expression, vessel formation, and proliferation of fibroblasts, keratinocytes, and pericytes. A similar stromal response was induced when α5 and α2 integrin subunits were overexpressed in the human dermis, suggesting that integrins play a major role in the induction of a transformed phenotype of fibroblasts by PDGF-B.