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GEN News Highlights : Jun 23, 2009

Scientists Discover Protein that Curbs Metastasis

Prosaposin works by preventing angiogenesis, according to PNAS paper.

Researchers at Children's Hospital Boston isolated a protein from tumor cells that blocks metastasis. Called prosaposin, this protein triggers production of factors that block the growth of blood vessels. The findings are published in this week’s online Early Edition of the Proceedings of the National Academy of Sciences.

Cells from localized prostate and breast tumors, which didn't metastasize, secreted high levels of prosaposin, while metastatic tumors secreted very little, according to the investigators. They then injected mice with highly metastatic tumor cells that had prosaposin added to them.

The scientists found that lung metastases were reduced by 80%, 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% longer than mice not receiving prosaposin.

Additionally, the researchers demonstrated that prosaposin stimulates activity of the well-known tumor suppressor p53 in the connective tissue surrounding the tumor. This in turn stimulated production of thrombospondin-1, a natural inhibitor of blood vessel growth, both in the tumor stroma and in cells at the distant location.



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