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

1)癌细胞队列迁移过程中细胞-细胞粘附的区室化释放机制研究结果表明，细胞下部细胞-细胞粘附的局部释放，允许细胞延伸前沿移动，可能受IQGAP1从细胞质转移到细胞膜及其与E-cadherin和catenin复合物形成的调控，随后从E-cadherin/catenin复合物中释放α -catenin。这一机制也可能与HGF/SF刺激和细胞外基质粘附信号之间的串扰有关，后者在细胞运动过程中调节细胞间的粘附。2) IQGAP1在人结肠癌组织中的表达单特异性抗IQGAP1抗体免疫组化研究显示，与正常结肠组织相比，IQGAP1在癌组织中的表达增强。IQGAP1在浸润前沿表达最为显著，并且在三分之二的深层癌组织中的表达程度明显高于三分之一的浅表癌组织。研究表明，IQGAP1参与结肠癌在体内的侵袭机制。3)迁移细胞片中MT1-MMP前细胞特异性表达通过细胞-细胞接触调控。利用MT1-MMP RNA探针进行原位杂交研究发现，迁移细胞片中MT1-MMP前细胞特异性表达受细胞-细胞接触调控，且调控是在mRNA水平上完成的。细胞间的接触及其信号不需要聚合肌动蛋白丝的形成和附着。研究还表明，细胞自身产生的纤维连接蛋白可能会刺激前细胞的MT1-MMP表达。

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.