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Mechanism found that 'protects' aggressive melanoma from angiogenesis inhibitors

Northwestern University researchers have discovered a mechanism that may help to explain how angiogenesis inhibitors work on normal, blood vessel-forming endothelial cells, but not on insidious, aggressive melanoma cells that masquerade as endothelial-like cells by forming their own vascular networks, called "vasculogenic mimicry."

Mary J. C. Hendrix, professor of pediatrics at Northwestern University Feinberg School of Medicine and president and scientific director of the Children's Memorial Research Center, led the study, results of which were published in the Oct. 6 issue of the Journal of the National Cancer Institute. Hendrix and her laboratory team are also members of The Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Hendrix and colleagues found that endostatin and two other angiogenesis inhibitors, which prevent new blood vessel growth that supports the spread of cancerous tumors, were effective in blocking endothelial cell formation of vascular networks, but were unable to prevent vascular networks formed by melanoma cells.

Further experiments showed that endothelial cells have more endostatin receptors than melanoma cells, suggesting a mechanistic basis for the differential response of the two cell types to angiogenesis inhibitors.

Findings from the study may contribute to the development of new cancer therapies that target both angiogenesis and tumor cell vasculogenic mimicry.

Moreover, because vasculogenic mimicry has been reported in several other tumor types, including breast, prostatic, ovarian and lung cancer, these findings may offer new insights for designing rational antivascular therapies in other forms of cancer, Hendrix said.

In the past decade, many new angiogenesis inhibitors have been identified, and several have been shown effective against tumor growth in laboratory experiments. However, results of early clinical trials with thes
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Contact: Elizabeth Crown
e-crown@northwestern.edu
312-503-8928
Northwestern University
7-Oct-2004


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