A Study on The Regulation of MMPs's Activities and Metastatic Potential of Colorectal cancer

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Our previous biochemical studies showed that plasmin can activate proMMP-3, and MMP-3 can activate proMMP-9 readily. Toclarify significance of MMP-9, MMP-3, u-PA and TIMP-1 expression in colorectal cancer tissues we investigated the expression of MMP-9, MMP-3, TIMP-1, and u-PA in human colorectal cancer and orthtopically inoculated colon cancer of nude mice.Immunohistochemistry and in situ hybridization demostrated that MMP-9 expressed by the tumor cells might play an important role in tumor development and progression, in particular in hematogenous metastasis in colorectal cancer, and that the balance between MMP-9 and TIMP-1 prodution in the tumor cells was important for liver metastasis from colon cancer. MMP-3 was observed in monocyte-macrophages and fibroblasis mainly at the tumor invasive front but not in the tumor cells. U-PA was noted mainly in the tumor cells, but the extent was variable. Both MMP-3 and u-PA tended to be co-expressed with MMP-9 at the tumor invasive front. In addition, both the incidence of MMP-3 and u-PA expression in tumor tissues in the cases with liver metastasis was significantly higher than in the cases without liver metastasis.We conclude that MM-3 expresed by momocyte-macrophages and u-PA expressed by tumor cells may act as direct or indirect actiator for proMMP-9.