Article
Lab Invest 2001, 81:1263–1274
5 and 2 Integrin Gene Transfers Mimic the PDGF-B–Induced Transformed Phenotype of Fibroblasts in Human Skin
This study was supported in part by National Institutes of Health (NIH) Grants CA25874, CA76674, CA74294, DK50306, and CA10815. HS was supported by the Austrian Science Foundation (FWF-1652-Med) and the Max Kade Foundation.
Mark Nesbit1,4, Helmut Schaider1,4, Carola Berking1, Daw-Tsun Shih1, Mei-Yu Hsu1, Michelle McBrian1, Timothy M Crombleholme2, Rosalie Elenitsas3, Clayton Buck1 and Meenhard Herlyn1
- 1The Wistar Institute, Philadelphia
- 2Department of Surgery, The Children's Hospital of Philadelphia, Philadelphia
- 3Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania
Correspondence: Dr. Meenhard Herlyn, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104. E-mail: HerlynM@Wistar.Upenn.edu
4MN and HS contributed equally to the study.
Received 6 June 2001.
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 
5 and 2 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 5 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 5 and 2 integrin subunit expression, vessel formation, and proliferation of fibroblasts, keratinocytes, and pericytes. A similar stromal response was induced when 5 and 2 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.
