PDGF-D is a potent transforming and angiogenic growth factor.
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.
Li
Hong
H
Ludwig Institute for Cancer Research, Stockholm Branch, Stockholm, Sweden.
Fredriksson
Linda
L
Li
Xuri
X
Eriksson
Ulf
U
D016475:3T3 Cells / Q000473:pathology; D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D043925:Angiogenesis Inducing Agents / Q000502:physiology*; D000818:Animals; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008222:Lymphokines; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000502:physiology; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay
D000199:Actins; D043925:Angiogenesis Inducing Agents; D008222:Lymphokines; C427493:PDGFD protein, human; C498951:Pdgfd protein, mouse; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C411423:platelet-derived growth factor C; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta