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EWS/FLI1 regulates tumor angiogenesis in Ewing's sarcoma via suppression of thrombospondins

Gary Potikyan1, Rupert O V Savene, Julie M Gaulden

  • 1Molecular Biology Institute, Jonsson Comprehensive Cancer Center, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90024, USA.

Cancer Research
|July 20, 2007
PubMed

Insights

Thrombospondins, natural angiogenesis inhibitors, are suppressed by EWS/FLI1 in Ewing sarcoma. Restoring thrombospondins reduced tumor growth and vascularization, indicating their therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Suppression of antiangiogenic factors is linked to malignancies.
  • Thrombospondins 1 and 2 are key inhibitors of angiogenesis regulated by oncogenes.

Purpose of the Study:

  • To investigate the role of thrombospondins in Ewing sarcoma.
  • To determine how EWS/ETS fusion oncoproteins regulate thrombospondins.

Main Methods:

  • Investigated EWS/FLI1 regulation of thrombospondins in cell lines.
  • Analyzed EWS/FLI1 DNA-binding domain and promoter interactions.
  • Assessed the impact of forced thrombospondin expression on tumor formation in vivo.

Main Results:

  • EWS/FLI1 fusion protein suppresses thrombospondin expression in Ewing sarcoma cells.
  • This suppression requires an intact EWS/FLI1 DNA-binding domain.
  • Forced thrombospondin expression inhibited tumor growth and reduced microvessel density in vivo.

Conclusions:

  • Thrombospondins play a significant role in Ewing sarcoma vascularization.
  • Targeting thrombospondin regulation offers potential therapeutic strategies for Ewing sarcoma.

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