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Potent metastasis inhibitor identified
Date:6/22/2009

Researchers at Children's Hospital Boston have isolated a potent inhibitor of tumor metastasis made by tumor cells, one that could potentially be harnessed as a cancer treatment. Their findings were published in the online Early Edition of the Proceedings of the National Academy of Sciences during the week of June 22.

Metastasisthe migration of cancer cells to other parts of the bodyis one of the leading causes of death from cancer, and there is no approved therapy for inhibiting or treating metastases. Randoph S. Watnick, PhD, an assistant professor in the Vascular Biology Program at Children's, has been finding that metastatic tumors prepare landing places in distant organs for their metastases, by secreting certain proteins that encourage tumor growth and attract feeder blood vessels. Now, he and his colleagues show that non-metastatic tumors secrete a protein called prosaposin -- which inhibits metastasis by causing production of factors that block the growth of blood vessels.

Cells from localized prostate and breast tumors, which didn't metastasize, secreted high levels of prosaposin, they found, while metastatic tumors secreted very little. When the researchers injected mice with tumor cells that were known to be highly metastatic, but to which they had added prosaposin, lung metastases were reduced by 80 percent and lymph node metastases were completely eliminated, and survival time was significantly increased. Conversely, when they suppressed prosaposin expression in tumor cells, they saw more metastases.

When prosaposin was directly injected into mice that had also received an injection of tumor cells, the tumor cells formed virtually no metastases in the lung, or, if they did, formed much smaller colonies. These mice lived at least 30 percent longer than mice not receiving prosaposin.

Watnick and colleagues also demonstrated that prosaposin stimulates activity of the well-known tumor suppressor p53 in the co
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Contact: Bess Andrews
elizabeth.andrews@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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