| Co-Investigator(Kenkyū-buntansha) |
HORI Hisae Tokyo Medical & Dental University, Medical Research Institute, Assistant Professor, 難治疾患研究所, 助手 (80014190)
YAMAMOTO Kazuhiko University of Tokyo, Hospital, Professor, 医学部付属病院, 教授 (80191394)
SEYAMA Yousuke University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90010082)
YOSHIMOTO Masataka Cancer Institute Hospital, Department of Breast Surgery, Chief, 外科, 副部長(研究職)
HATTORI Shunji Nippi Biomatrix Institute, Chief Researcher, 主任研究員
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| Research Abstract |
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.
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