PDGF-D Is a Potent Transforming and Angiogenic Growth Factor

Oncogene. 2003 Mar 13;22(10):1501-10. doi: 10.1038/sj.onc.1206223.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells / pathology
  • Actins / metabolism
  • Actins / 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
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Tumor Stem Cell Assay

Substances

  • 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