Expression and localization of membrane-type-1 matrix metalloproteinase, CD 44, and laminin-5?2 chain during colorectal carcinoma tumor progression

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• 作者：Shinji Murai ; Toshifumi Umemiya ; Motoharu Seiki and Kenichi Harigaya
• 关键词：MT1 ; MMP ; CD44 ; LN ; 52 ; ; Catenin ; Colorectal carcinoma
• 刊名：Virchows Archiv
• 出版年：2004
• 出版时间：September 2004
• 年：2004
• 卷：445
• 期：3
• 页码：271-278
• 全文大小：727 KB

文摘

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-52 chain (LN-52) monomer, in 48 cases of colorectal tumors. Recent studies have shown that MT1-MMP, CD44 and LN-52 are direct downstream targets in the adenomatosis polyposis coli (APC)/-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-52 monomers at the invasive front of dedifferentiated tumor cells. Additionally, the graded expression of nuclear active -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.