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[Cancer Research 61, 5778-5783, August 1, 2001]
© 2001 American Association for Cancer Research

Experimental Therapeutics

Growth Inhibition of Dermatofibrosarcoma Protuberans Tumors by the Platelet-derived Growth Factor Receptor Antagonist STI571 through Induction of Apoptosis

Tobias Sjöblom1, Akira Shimizu1,, 2, Kevin P. O’Brien3, Kristian Pietras, Paola Dal Cin4, Elisabeth Buchdunger, Jan P. Dumanski5, Arne Östman and Carl-Henrik Heldin6

Ludwig Institute for Cancer Research, S-751 24 Uppsala, Sweden [T. S., A. S., K. P. O., A. Ö., C-H. H.]; Department of Molecular Medicine, Clinical Genetics Unit, Karolinska Hospital, S-171 76 Stockholm, Sweden [K. P. O., J. P. D.]; Centre for Human Genetics, University of Leuven, B-3000 Leuven, Belgium [P. D. C.]; and Novartis Pharma AG, Oncology Research, CH-4002 Basel, Switzerland [E. B.]

Dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) are recurrent, infiltrative skin tumors that presently are treated with surgery. DFSP and GCF tumors are genetically characterized by chromosomal rearrangements fusing the collagen type I{alpha}1 (COLIA1) gene to the platelet-derived growth factor B-chain (PDGFB) gene. It has been shown that the resulting COL1A1/PDGF-B fusion protein is processed to mature PDGF-BB. Autocrine PDGF receptor stimulation has therefore been predicted to contribute to DFSP and GCF tumor development and growth. Here we demonstrate presence of activated PDGF receptors in primary cultures derived from six different DFSP and GCF tumors. Three of the primary cultures were further characterized; their in vitro growth displayed an increased sensitivity to treatment with the PDGF receptor tyrosine kinase inhibitor STI571, as compared with normal fibroblasts. Transplantable tumors, displaying a DFSP-like histology, were established from one of the DFSP primary cultures. Treatment of tumor-bearing severe combined immunodeficient mice with STI571 reduced tumor growth. The growth-inhibitory effects in vitro and in vivo occurred predominantly through induction of tumor cell apoptosis. Our study demonstrates growth-inhibitory effects of PDGF receptor antagonists on human DFSP- and GCF-derived tumor cells and demonstrates that autocrine PDGF receptor stimulation provides antiapoptotic signals contributing to the growth of these cells. These findings suggest targeting of PDGF receptors as a novel treatment strategy for DFSP and GCF.




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[Abstract] [Full Text] [PDF]

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