“Although many men develop prostate cancer, it is difficult to identify the men whose cancer will metastasize and become resistant to hormone therapy,” says Michael Caterina, M.D., Ph.D., a 2012 Patrick C. Walsh Prostate Cancer Research Fund recipient. But now, he believes he has an important new clue: A protein that controls the calcium levels within a cell.
The protein in question is named Transient Receptor Potential Vanilloid 2 (TR PV2). Recently, scientists found that the very worst kinds of prostate cancer cells make more of this protein than other cancer cells. TR PV2 “functions essentially as a selective door that can open and close to allow calcium ions to enter cells,” Caterina explains. Calcium levels inside cells control many processes, including movement and migration, gene expression, and secretion of hormones and enzymes. Now scientists have shown that when they lower the production of TR PV2 in aggressive prostate cancers, “not only can they reduce the flow of calcium into these cells, but they can also reduce the tendency of these cells to migrate.”
Caterina believes that the flow of calcium through TR PV2 might be the trigger for cancer cells to migrate out of the prostate. Their mode of escape? They seem to chew their way out. “In order to escape the prostate, cancer cells must digest a web of proteins that confine them there,” says Caterina. “Here again, TR PV2 might be important, because research shows that prostate cancer cells lacking TR PV2 make fewer protein-digesting enzymes than those with TR PV2. Given these tantalizing observations, we plan to ask two questions. First, is TR PV2 expression truly greater in those human prostate cancers that are more aggressive?” To answer this question, Caterina and co-investigator Tamara Lotan, M.D. plan to take advantage of a vast repository of prostate tumor samples from human patients.
Their mode of escape? They seem to chew their way out.
“In order to escape the prostate, cancer cells must digest a
web of proteins that confine them there.”
Using antibodies that detect TR PV2 specifically, “we will ask whether this protein is indeed expressed at the highest levels in those tumors that exhibit a more aggressive nature, and whether the expression level of TR PV2 can be used as a predictor of which patients will fare the worst.”
The second question: “Can we take advantage of mice recently generated in our lab that lack TR PV2?” The investigators hope the mice will help them study in greater detail the contributions of this protein to the onset and progression of prostate cancer. They plan to cross mice lacking TR PV2 with another strain of mice lacking a different protein, called PTEN . “Mice lacking PTEN spontaneously develop prostate cancer at a rate much higher than normal,” Caterina explains. Also, the PTEN protein is known to degrade a chemical that normally activates TR PV2. “We predict that the removal of TR PV2 might slow or reduce the development of aggressive tumors in the PTEN mutant mice.” One result of this work might be finding new ways to identify men with potentially deadly cancer who need aggressive therapy. Caterina also hopes this work will lead to “development of better therapies that specifically block the ability of prostate cancer cells to escape the prostate and invade other tissues.”