Enzyme Linked to Aggressive Prostate Cancer

The enzyme mesotrypsin, also known as protease, serine 3 (PRSS3), is specifically associated with aggressive prostate cancer risk.

Mesotrypsin appears to be an important mediator of prostate cancer progression and metastasis, and it has been suggested that inhibition of mesotrypsin activity may provide a novel modality for prostate cancer treatment.

Cancer biologists at the Mayo Clinic (Jacksonville, Florida, USA) explored whether any other cancer abnormally expresses the enzyme PRSS3 and when this occurred. They gathered and analyzed data from several sources. They used various techniques including cell culture, ribonucleic acid (RNA) extraction and polymerase chain reaction (PCR), bioluminescent imaging, and immunohistochemistry.

By transcriptional profiling, the investigators identified a correlation between PRSS3 gene expression and prostate cancer progression in a microarray dataset in which five benign prostate, five clinically localized prostate cancer, and five metastatic prostate cancer tissue specimens. They found that PRSS3 expression in tumors was strikingly associated with recurrence, defined as systemic progression or rising prostate specific antigen. The association of PRSS3 with prostate cancer metastasis, and the evidence that PRSS3 expression in primary tumors is prognostic of recurrence, suggest that mesotrypsin may play a critical functional role in prostate cancer progression.


Evette Radisky, PhD, the senior investigator, said, "This molecule is a protease, which means it digests other molecules. Our data suggests PRSS3 activity changes the environment around prostate cancer cells, perhaps by freeing them from surrounding tissue to promote malignancy and invasiveness. I do not think PRSS3 is the only factor involved in driving aggressive prostate cancer, but it may be significant for a certain subset of this cancer, the kind that is potentially lethal. Prostate cancer patients could be tested for the presence of the enzyme, so that doctors could identify which ones had the highest risk of metastasis." The study was published on December 17, 2012, in the journal Molecular Cancer Research.

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