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

MMPs活性调控与结直肠癌转移潜能的研究

基本信息

批准号：
07671440
负责人：
OGATA Yutaka
金额：
$ 1.34万
依托单位：
Kurume University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671440/
关键词：
Colorectal Cancer Liver Metastasis Orthotopic Inoculated Colon Cancer Matrix Metalloproteinase 9 Matrix Metalloproteinase 3 Urokinese Type Plasminogen Activator Tissue INhibitor of Metalloproteinase 1 Matrix Metalloprcteinase9 Matrix Metal

项目摘要

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.

我们之前的生化研究表明，纤溶酶可以激活proMMP-3，而MMP-3可以很容易地激活proMMP-9。为了明确结直肠癌组织中MMP-9、MMP-3、u-PA和TIMP-1表达的意义，我们检测了人结直肠癌和裸鼠原位接种结肠癌中MMP-9、MMP-3、TIMP-1和u-PA的表达。免疫组化和原位杂交表明肿瘤细胞表达MMP-9可能 MMP-9 和 TIMP-1 在肿瘤的发生和进展中发挥着重要作用，特别是在结直肠癌的血行转移中，肿瘤细胞中 MMP-9 和 TIMP-1 的产生之间的平衡对于结肠癌的肝转移非常重要。 MMP-3主要在肿瘤侵袭前沿的单核巨噬细胞和成纤维细胞中观察到，但在肿瘤细胞中没有观察到。 U-PA 主要存在于肿瘤细胞中，但程度各异。 MMP-3 和 u-PA 均倾向于与 MMP-9 在肿瘤侵袭前沿共表达。此外，肝转移病例肿瘤组织中MMP-3和u-PA表达的发生率均显着高于无肝转移病例。我们推测单核巨噬细胞表达的MM-3和肿瘤细胞表达的u-PA可能是proMMP-9的直接或间接激活剂。