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PDGF-D is a potent transforming and angiogenic growth factor.

Abstract
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.
AuthorsHong Li, Linda Fredriksson, Xuri Li, Ulf Eriksson
JournalOncogene (Oncogene) Vol. 22 Issue 10 Pg. 1501-10 (Mar 13 2003) ISSN: 0950-9232 [Print] England
PMID12629513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actins
  • Angiogenesis Inducing Agents
  • Lymphokines
  • PDGFD protein, human
  • Pdgfd protein, mouse
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • platelet-derived growth factor C
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta
Topics
  • 3T3 Cells (pathology)
  • Actins (metabolism, ultrastructure)
  • Angiogenesis Inducing Agents (physiology)
  • Animals
  • Carcinogenicity Tests
  • Cell Division (genetics)
  • Cell Transformation, Neoplastic
  • Down-Regulation
  • Female
  • Gene Expression Regulation
  • Humans
  • Lymphokines
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Pathologic
  • Platelet-Derived Growth Factor (physiology)
  • Proto-Oncogene Proteins c-sis (physiology)
  • Receptor, Platelet-Derived Growth Factor alpha (genetics, metabolism)
  • Receptor, Platelet-Derived Growth Factor beta (genetics, metabolism)
  • Tumor Stem Cell Assay

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