Platelet-derived
growth factors (PDGFs) are important for normal tissue growth and maintenance. Overexpression of the classical PDGFs,
PDGF-A and PDGF-B, has been linked to several diseases, including
cancer, fibrotic disease and
atherosclerosis. Recently, two novel PDGFs,
PDGF-C and PDGF-D, were discovered. It has not yet been established whether
PDGF-C and PDGF-D are linked to disease phenotypes like the classical PDGFs. PDGF-B, the cellular homologue of the viral simian
sarcoma oncogene v-sis, is known to potently induce cellular transformation through activation of
PDGF receptor (
PDGFR)-beta. In this work, we have determined the transformation efficacy of PDGF-D in comparison with that of
PDGF-C and PDGF-B. PDGF-D is a potent
transforming growth factor for NIH/3T3 cells, and the transformed cells displayed stress fibre reorganization, increased proliferation rate, anchorage-independent growth in soft
agar, ability to induce tumours in nude mice, and upregulation of
vascular endothelial growth factor. Morphological analyses of the vasculatures from the PDGF-
isoform-expressing tumours revealed marked differences suggesting differential signalling through the two
PDGF receptors in tumour vessel development and remodelling. In summary, these results suggest that PDGF-D induce cellular transformation and promote tumour growth by accelerating the proliferation rate of the tumour cells, and by stimulation of tumour neovascularization.