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PDGF-D is a potent transforming and angiogenic growth factor

Oncogene volume 22, pages 1501–1510 (2003)Cite this article

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)-β. 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.

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Acknowledgements

We thank Barbara Åkerblom for expert technical assistance and Kristian Pietras and Arne Östman for kindly providing us with PDGF-BB protein and PDGF receptor antibodies. This study was supported by the Swedish Research Council, the Novo Nordisk Foundation, and Karolinska Institutet.

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  1. Ludwig Institute for Cancer Research, Stockholm Branch, Box 240, Stockholm, S-171 77, Sweden

    Hong Li, Linda Fredriksson, Xuri Li & Ulf Eriksson

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  1. Hong Li
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Correspondence to Ulf Eriksson.

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Li, H., Fredriksson, L., Li, X. et al. PDGF-D is a potent transforming and angiogenic growth factor. Oncogene 22, 1501–1510 (2003). https://doi.org/10.1038/sj.onc.1206223

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