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

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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.