Alpha5 and alpha2 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 transforming fibroblasts. Using adenoviral vectors, we tested whether endogenous PDGF-B expression in human skin xenotransplants leads to changes in the expression of alpha5 and alpha2 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 alpha5 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 alpha5 and alpha2 integrin subunit expression, vessel formation, and proliferation of fibroblasts, keratinocytes, and pericytes. A similar stromal response was induced when alpha5 and alpha2 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.
Nesbit
M
M
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Schaider
H
H
Berking
C
C
Shih
D T
DT
Hsu
M Y
MY
McBrian
M
M
Crombleholme
T M
TM
Elenitsas
R
R
Buck
C
C
Herlyn
M
M
D015703:Antigens, CD / Q000235:genetics* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D018014:Gene Transfer Techniques; D006801:Humans; D039421:Integrin alpha2; D039482:Integrin alpha5; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics* / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D012879:Skin Physiological Phenomena; D014161:Transduction, Genetic
D015703:Antigens, CD; D039421:Integrin alpha2; D039482:Integrin alpha5; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020574:Proto-Oncogene Proteins c-sis