Breaking the Chain of Metastasis                

If the cells that are found early on, when cancer is confined to the prostate, somehow wanted to leave the home base and establish themselves in distant sites, they couldn’t do it. They wouldn’t be up to the task of traveling and breaking new ground. "In order for prostate cancer cells to metastasize, a lot of things have to happen," says bioscientist Michael Caterina, M.D., Ph.D. "They must change their shape, escape the prostate, and migrate to other tissues." All of these little challenges, which metastatic cancer cells manage to overcome, are potential targets for treatment – individual links that could disrupt a whole chain of events.

With urologic pathologist Tamara Lotan, M.D., Caterina is studying one potential link in the chain of metastatic prostate cancer, an ion channel protein called TRPV2. First, Caterina and Lotan demonstrated the presence of TRPV2 in three different cell lines of human prostate cancer. Then, using commercial antibodies that recognize TRPV2, "we stained a human prostate sample that contained both normal tissue and a relatively low-grade prostate tumor," says Caterina. "Interestingly, the signal from these antibodies exhibited a greater intensity in the normal prostate cells than in the tumor. Although we cannot yet be certain that it is truly the TRPV2 protein that is being detected, this result suggests that we have much to learn regarding the relationship between TRPV2 and tumor aggressiveness." To find out more, the scientists have begun to cross mice that lack this protein with another line of mice that tend to form aggressive prostate tumors, "so that we can directly evaluate the importance of TRPV2 to tumor progression." Caterina and Lotan also have custom-manufactured antibodies in the lab that recognize both human and mouse TRPV2, "so that we can learn more about whether, and how, TRPV2 contributes to aggressive prostate cancer in mice and in humans." This work was supported by the Patrick C. Walsh Prostate Cancer Research Fund.

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