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[Cancer Research 59, 5536-5541, November 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 5536-5541, November 1, 1999]
© 1999 American Association for Cancer Research

Experimental Therapeutics

Inhibition of Angiogenesis by Blocking Activation of the Vascular Endothelial Growth Factor Receptor 2 Leads to Decreased Growth of Neurogenic Sarcomas1

Lilyana Angelov, Bodour Salhia, Luba Roncari, Gerald McMahon and Abhijit Guha2

Division of Neurosurgery [L. A., A. G.] and The Peripheral Nerve Clinic [A. G.], Toronto Western Hospital, University of Toronto, Toronto, Canada M5T 2S8; Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada M5G 1X5 [L. A., B. S., L. R., A. G.]; and SUGEN, Inc., South San Francisco, California 94080 [G. M.]

Neurogenic sarcomas are incurable, common malignant human peripheral nerve tumors subject to local recurrence and systemic metastasis. In this study, the vascularity, vascular endothelial growth factor (VEGF) expression, and effects of inhibiting VEGF receptor on growth of neurogenic sarcomas were examined. Vascularization and VEGF expression were 6.4- and 15-fold higher in tumors than in normal nerves. The small molecule inhibitor (SU5416) of VEGF receptor 2 had no effect on neurogenic sarcoma cell lines in vitro, but the growth of a human tumor explant xenograft model was reduced by 54.8% compared to vehicle. Reduction in tumor growth was due to decreased tumor angiogenesis, leading to reduction of tumor cell proliferation and increased apoptosis. Inhibiting VEGF function may therefore be a useful adjuvant therapy for neurogenic sarcomas.




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Copyright © 1999 by the American Association for Cancer Research.