Matrix metalloproteinase-2 and -9 in the urine of prostate cancer patients.

The matrix metalloproteinase family of enzymes is comprised of critically important extracellular proteases whose activity has been implicated in a number of key normal and pathological processes. The latter include growth, progression and metastasis as well as dysregulated angiogenesis that is associated with these events. The MMPs are secreted by all types of cells, and they also carve through the extracellular matrix, allowing cancer cells to take root and metastasize. Endogenous inhibitors typically hold MMPs in check but in cancer, the balance shifts against the inhibitors and in favor of MMPs, which ultimately spill over from blood into urine. By gelatin zymography we verified MMP activity in concentrated urine of patients with prostate disease. Of these patients, 30 had cancer, consisting of 13 with Gleason score 6, 12 with Gleason 7, 2 with Gleason 8, 3 with Gleason 9 and 8 had benign prostate hyperplasia. Zymography showed 4 dominant gelatinolityc bands of 240, 130, 92 and 72 kDa in prostate disease. The most abundant lytic activity is at 92 kDa (MMP-9), whereas MMP-2 is present in lesser quantities. Moreover, MMP-9 activity is enhanced in the urine from patients with benign prostate hyperplasia compared with cancer patients. No correlation between gelatinolytic activity and Gleason score or pathological findings was found.