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MGH study identifies new inhibitor of tumor angiogenesis and growth

A research team based at the Massachusetts General Hospital (MGH) has shown that a natural factor called thrombospondin-2 (TSP-2) inhibits the development of certain tumors in a mouse model by preventing the development of blood vessels, a process called angiogenesis. TSP-2 now joins a growing list of anti-angiogenesis factors being studied and in some instances tested as possible anti-cancer drugs. The report from the MGH Cutaneous Biology Research Center (CBRC) appears in the Dec. 21 issue of Proceedings of the National Academy of Sciences.

"We have found a natural factor that inhibits angiogenesis in normal tissues and, when reintroduced into tumor cells, stops tumor growth," says Michael Detmar, MD, who led the study. Detmar notes that some of the other anti-angiogenesis factors currently being studied do not appear to be involved in normal blood vessel development but instead are produced when other substances in the body break down. "We believe that TSP-2 is part of a natural protein system designed to prevent the development of malignant tumors," he adds.

TSP-2 is one of a group of proteins that help regulate the proliferation and development of several types of cells. It is structurally similar to thrombospondin-1 (TSP-1), a known angiogenesis inhibitor. Although the two proteins are produced at different times during development and in different tissues, both appear at high levels in developing blood vessels, suggesting an important role in the regulation of angiogenesis. While TSP-1 had previously been shown to inhibit angiogenesis and tumor growth, TSP-2's exact biological role had been unclear. The current study not only verifies TSP-2's activity in suppressing tumor growth and angiogenesis, it also shows that expression of both proteins completely stopped growth of the tumors studied in this project.

The researchers introduced TSP-2 DNA into cultured cells from human squamous cell carcinomas - tumors that do not normally produ
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Contact: Susan McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
20-Dec-1999


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