Researchers at Children's Hospital Boston have isolated a potent inhibitor of tumour metastasis made by tumour cells, one that could potentially be harnessed as a cancer treatment. Metastasis-the migration of cancer cells to other parts of the body-is 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 tumours prepare landing places in distant organs for their metastases, by secreting certain proteins that encourage tumour growth and attract feeder blood vessels. Now, he and his colleagues show that non-metastatic tumours secrete a protein called prosaposin -- which inhibits metastasis by causing production of factors that block the growth of blood vessels.

Cells from localised prostate and breast tumours, which didn't metastasize, secreted high levels of prosaposin, they found, while metastatic tumours secreted very little. When the researchers injected mice with tumour 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 tumour cells, they saw more metastases.

When prosaposin was directly injected into mice that had also received an injection of tumour cells, the tumour 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 tumour suppressor p53 in the connective tissue (stroma) surrounding the tumour. This in turn stimulated production of thrombospondin-1, a natural inhibitor of blood vessel growth (angiogenesis), both in the tumour stroma and in cells at the distant location.

"Prosaposin, or derivatives that stimulate p53 activity in a similar manner in the tumor stroma, might be an effective way to inhibit the metastatic process in humans," says Watnick.

If this bears out, Watnick envisions treating cancer patients for their primary tumour, and concurrently giving them drugs to prevent metastases or slow their growth. "While we may not be able to keep patients from getting cancer, we can potentially keep them metastasis-free," he says.

Children's Hospital Boston