This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Potikyan, G. Articles by Denny, C. T. Search for Related Content PubMed PubMed Citation Articles by Potikyan, G. Articles by Denny, C. T.

EWS/FLI1 Regulates Tumor Angiogenesis in Ewing's Sarcoma via Suppression of Thrombospondins

¹ Molecular Biology Institute and ² Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California; ³ Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and ⁴ The Department of Oncological Sciences, University of Utah School of Medicine, Salt Lake City, Utah

Requests for reprints: Christopher T. Denny, Department of Pediatrics, University of California, 10833 Le Conte Avenue, Los Angeles, CA 90024. Phone: 310-825-0704; Fax: 310-206-8089; E-mail: cdenny{at}ucla.edu.

Suppression of the expression of antiangiogenic factors has been closely associated with multiple malignancies. Thrombospondins 1 and 2 are members of a family of angiogenic inhibitors that are regulated by several oncogenes. In this study, we investigate the role of thrombospondins in Ewing's sarcoma and their regulation by EWS/ETS fusion oncoproteins. We show that the EWS/FLI1 fusion suppresses the expression of thrombospondins in both NIH3T3 fibroblasts and Ewing's sarcoma tumor–derived cell lines. This regulation depends on an intact EWS/FLI1 DNA-binding domain and may involve direct interactions between EWS/FLI1 and thrombospondin promoter regions. Forced expression of thrombospondins in Ewing's sarcoma cell lines inhibited the rate of tumor formation in vivo and markedly decreased the number of microvessels present in the tumors. These findings suggest that thrombospondins play a biologically significant role in tumor vascularization in Ewing's sarcoma and suggest potential therapeutic strategies for future therapeutic intervention. [Cancer Res 2007;67(14):6675–84]

This article has been cited by other articles:

				K. Wakahara, T. Ohno, M. Kimura, T. Masuda, S. Nozawa, T. Dohjima, T. Yamamoto, A. Nagano, G. Kawai, A. Matsuhashi, et al. EWS-Fli1 Up-Regulates Expression of the Aurora A and Aurora B Kinases Mol. Cancer Res., December 1, 2008; 6(12): 1937 - 1945. [Abstract] [Full Text] [PDF]