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Analysis of mechanisms involved in MMP localization and compartmentalized release from cell-cell adhesion during cohort migration of human colon carcinoma cells

人结肠癌细胞群体迁移过程中 MMP 定位和细胞粘附区室化释放所涉及的机制分析

基本信息

批准号：
12670210
负责人：
NABESHIMA Kazuki
金额：
$ 1.6万
依托单位：
Miyazaki Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670210/
关键词：
cancer invasion metastasis cell migration HGF SF cohort migration matrix metalloproteinases (MMP)

项目摘要

1) Mechanisms of a compartmentalized release from cell-cell adhesion during cohort migration of carcinoma cellsOur results have shown that a localized release from cell-cell adhesion in the lower portion of cells, which allows cells to extend leading edges to move, is possibly regulated by translocation of IQGAP1 from cytosol to cell membranes and its complex formation with E-cadherin and catenins there, with a consequent release of alpha-catenin from the E-cadherin/catenin complex. This mechanism might also be involved in a crosstalk between signals from HGF/SF stimulation and cell-ECM (extracellular matrix) adhesion, which regulates cell-cell adhesion during cell movement.2) IQGAP1 expression in human colon carcinoma tissuesImmunohistochemcial study with monospecific anti-IQGAP1 antibody has revealed enhanced expression of IQGAP1 in carcinoma tissue compared with that in normal colon tissue. IQGAP1 was expressed most prominently at the invasion front, and the extent of expression was significantly more in the deeper two-thirds of the carcinoma tissue than the superficial one-third. Involvement of IQGAP1 in mechanisms for colon cancer invasion in vivo was indicated.3) Regulation of front cell-specific expression of MT1-MMP via cell-cell contact in migrating cell sheetsAn in situ hybridization study with an MT1-MMP RNA probe has revealed that front cell-specific expression of MT1-MMP in migrating cell sheets is regulated by cell-cell contact and the regulation is done at the mRNA level. The cell-cell contact and its signals do not need formation of and attachment to polymerized actin filaments. It is also shown that MT1-MMP expression at front cells is possibly stimulated by fibronectin produced by ceils themselves.

1)癌细胞群迁移过程中细胞-细胞粘附的区室化释放机制我们的结果表明，细胞下部细胞-细胞粘附的局部释放，允许细胞延伸前缘以移动，可能是由IQGAP 1从胞质溶胶易位到细胞膜及其与E-钙粘蛋白和连环蛋白的复合物形成所调节的，随后从E-钙粘蛋白/连环蛋白复合物中释放α-连环蛋白。这一机制也可能参与了HGF/SF刺激信号与细胞-ECM（细胞外基质）粘附之间的串扰，从而调节细胞运动过程中的细胞-细胞粘附。2）IQGAP 1在人结肠癌组织中的表达使用单特异性抗IQGAP 1抗体的免疫组化研究显示，与正常结肠组织相比，IQGAP 1在癌组织中的表达增强。IQGAP 1在浸润前沿表达最显著，表达程度在深2/3的癌组织中显著高于浅1/3。3）迁移细胞片层中MT 1-MMP的前细胞特异性表达通过细胞-细胞接触进行调节用MT 1-MMP RNA探针进行的原位杂交研究表明，迁移细胞片层中MT 1-MMP的前细胞特异性表达受到细胞-细胞接触的调节，并且这种调节是在mRNA水平上进行的。细胞与细胞之间的接触及其信号传递不需要肌动蛋白聚合丝的形成和附着。细胞自身产生的纤连蛋白可能刺激前细胞的MT 1-MMP表达。