Expression and localization of membrane-type-1 matrix metalloproteinase, CD 44, and laminin-5gamma2 chain during colorectal carcinoma tumor progression.

Membrane-type-1 matrix metalloproteinase (MT1-MMP) is overexpressed in many malignant tumor tissues and would be involved in tumor-cell migration. Using dual immunofluorescence of frozen sections, this study examined the expression and localization of MT1-MMP and its interacting molecules, CD44 and laminin-5gamma2 chain (LN-5gamma2) monomer, in 48 cases of colorectal tumors. Recent studies have shown that MT1-MMP, CD44 and LN-5gamma2 are direct downstream targets in the adenomatosis polyposis coli (APC)/beta-catenin (Wnt)-signaling pathway, which is upregulated in most colorectal epithelial tumors. MT1-MMP overexpression was observed in adenocarcinoma cases with moderate and/or less differentiation coinciding with CD44 downmodulation. Recent observations indicate that MT1-MMP overexpression disrupts tubulogenesis of MDCK cells in type-I collagen-rich tissues. Therefore, MT1-MMP overexpression might involve disturbances of neoplastic glandular structures during colorectal adenocarcinoma tumor progression. Intensity distribution analyses of images with dual immunofluorescence indicated that overexpressed MT1-MMP is closely associated with the enhanced expression of the LN-5gamma2 monomers at the invasive front of dedifferentiated tumor cells. Additionally, the graded expression of nuclear active beta-catenin was found in moderately differentiated and dedifferentiated areas of adenocarcinomas, where MT1-MMP overexpression was observed. Therefore, this study reveals that MT1-MMP might be a major effector of Wnt signaling in the late stage of colorectal carcinoma tumor progression.