Castration-resistant prostate cancer-specific protease: Function analysis and application search as a therapeutic target.

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Protease activities in culture media of prostate cancer cells were measured using 95 dipeptidyl substrates and a hydrolytic activity for Ac-XZ-MCA was found in media of castration-resistant but not -sensitive type cells. This activity was completely inhibited by DFP but not by other inhibitors, indicating this protease is serine-type. This activity was much higher in the washed cell suspensions than the culture supernatants and was localized on the cancer cell membrane when stained using biotin-XZ-chloromethylketone, which revealed that this protease is not secreted to the media but bound to the cell membrane. This protease was separated from the cell membrane and subjected to proteomics analysis but has not been identified because of a small amount of the protease. This castration-resistant prostate cancer cell-specific protease is a promising therapeutic target, thus further purification procedures will be done for its identification.