Establishment of Quantitative Method for Measurement of MMPs in Blood and Bile, and Its Clinical Application

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We have established quantitative method for the measurement of MMPs, especially MMP-2 and MMP-9 in blood and bile. We applied this method to clinical samples, and found the following new results.(1)MMP-9 levels in blood was significantly elevated in gastric cancer patients, compared to normal healthy subjects. In stage IV gastric cancer patients MMP-9 level was the highest among stages I, II, III and IV.We examined the correlation between MMP-9 level and the survival of gastric cancer patients, and found that the level of MMP-9(>410)was a good indicator for predicting the survival of gastric cancer patients.(2)We for the first time established a method for measuring MMP-2 and MMP-9 in bile. Further, we have found that activated MMP-2 and proMMP-9 activities were good markers for predicting liver metastasis in colon cancer patients.Immunohistochemical analysis using anti-MMP-2 antibody was performed in various cancer tissue sections and we found that MMP-2 expressed in 59% cases out of 80 various cancer including colon, uterus, lung, liver brain, soft tissue and esophagus. We for the first time found that MMP-2 expression was transcriptionally controlled by ODC in cancer cells using gel shift and promotor assays. As ODC is now considered to be a protooncogene and expresses in various cancer, the results suggest that suppressing ODC expression is a reasonabale approach to treat cancer and metastasis.