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Scientists have discovered that a molecule called hepsin promotes the deadly progression of prostate cancer. This research may lead to development of new therapeutics designed to decrease the spread of prostate cancer by specifically inhibiting hepsin. The study is published in the August issue of Cancer Cell.
The spread of cancer from its site of origin to another location in the body is called metastasis. If metastasis not controlled, it often results in death. Therefore, understanding the complex mechanisms that contribute to metastasis is critical for the design of therapeutics that can effectively combat cancer.
Proteins called proteases play an important role in the maintenance of proper tissue organization, and abnormal regulation of proteases has been implicated in the spread of cancer. Levels of the cell surface protease hepsin are markedly increased in human prostate cancer. To examine the functional significance of excess hepsin, Dr. Valeri Vasioukhin from the Fred Hutchinson Cancer Research Center in Seattle, Washington and colleagues generated mice with elevated hepsin levels in the prostate gland. The mice with elevated hepsin levels had marked disorganization of the prostate gland, specifically of a key structure called the basement membrane that separates different populations of cells. Disorganization and disruption of the basement membrane is a mandatory step that occurs early in the metastasis process.
Importantly, when hepsin was overexpressed in a mouse model of non-metastasizing prostate cancer, the mice developed more advanced prostate tumors and prominent metastases in the liver, lung, and bone. These data provide strong evidence that hepsin promotes prostate cancer progression and metastasis.
"We have found that increase in hepsin expression leads to disorganization of the basement membrane and promotes primary prostate cancer progression and metastasis," says Dr. Vasioukhin. "Since hepsin is an enzyme, it should be relatively easy to develop drugs specifically inhibiting hepsin activity. Previous research demonstrated that hepsin is not critical for normal cells within the body and, therefore, inhibition of hepsin with drugs is unlikely to have significant side effects." The researchers conclude that hepsin is a metastasis-promoting protein and suggest that it may provide an excellent therapeutic target to prevent tumor progression and metastasis in prostate cancer patients.
Olga Klezovitch, John Chevillet, Janni Mirosevich, Richard L. Roberts, Robert J. Matusik, and Valeri Vasioukhin: "Hepsin promotes prostate cancer progression and metastasis"
Publishing in Cancer Cell, Volume 6, Issue 2, August 2004, pages 185-195.
Journal
Cancer Cell