alpha 5 and alpha 2 integrin gene transfers mimic the PDGF-B-induced transformed phenotype of fibroblasts in human skin

Platelet-derived growth factor (PDGF)-B is a proto-oncogene capable of tran sforming fibroblasts. Using adenoviral vectors, we tested whether endogenou s PDGF-B expression in human skin xenotransplants leads to changes in the e xpression of alpha5 and alpha2 integrin subunits and whether integrin overe xpression leads to PDGF-related changes in the skin. In vitro, transduction of fibroblasts with PDGF-B or the integrin alpha5 subunit stimulated multi layered growth and spindle-type morphology, both markers of mesenchymal cel l transformation. In vivo, PDGF-B transduction of the human dermis was asso ciated with up-regulation of collagen and fibronectin synthesis, increases in alpha5 and alpha2 integrin subunit expression, vessel formation, and pro liferation of fibroblasts, keratinocytes, and pericytes. A similar stromal response was induced when alpha5 and alpha2 integrin subunits were overexpr essed in the human dermis, suggesting that integrins play a major role in t he induction of a transformed phenotype of fibroblasts by PDGF-B.