Leeman Matthew F, Curran Stephanie, Murray Graeme I
Department of Pathology, University of Aberdeen, Aberdeen, UK.
J Pathol. 2003 Dec;201(4):528-34. doi: 10.1002/path.1466.
This review outlines new concepts that are emerging for the functions of matrix metalloproteinases in colorectal cancer development and progression. The two main concepts that will be discussed are the role of matrix metalloproteinases in the early stages of colorectal tumour development and the functional mechanisms by which matrix metalloproteinases contribute to colorectal tumour invasion and metastasis. The matrix metalloproteinases are a group of enzymes, which have been best characterized for their ability to degrade extracellular matrix proteins and thus they have been extensively studied in tumour invasion. It is now becoming recognized that the matrix metalloproteinases have key roles in a variety of biological processes that are distinct from their well-defined role in matrix degradation. This group of enzymes has been shown to interact with a broad range of non-matrix proteins including growth factors and their receptors, mediators of apoptosis, and cell adhesion molecules. The elucidation of novel biological roles for the matrix metalloproteinases also challenges the current predominant concept of matrix metalloproteinases as enzymes only involved in matrix degradation. Recent studies have shown that several matrix metalloproteinases, especially matrilysin (MMP-7), interact with the specific molecular genetic and signalling pathways involved in colorectal cancer development. In particular, matrilysin is activated at an early stage of colorectal tumourigenesis by the beta-catenin signalling pathway. Furthermore, studies are now elucidating specific mechanisms by which individual matrix metalloproteinases, especially membrane-type matrix metalloproteinases, interact with specific cell adhesion molecules and cytoskeletal proteins and thus contribute dynamically to colorectal tumour invasion.
本综述概述了基质金属蛋白酶在结直肠癌发生和发展过程中所呈现的新功能概念。将讨论的两个主要概念是基质金属蛋白酶在结直肠肿瘤发生早期的作用，以及基质金属蛋白酶促进结直肠肿瘤侵袭和转移的功能机制。基质金属蛋白酶是一组酶，其最显著的特点是能够降解细胞外基质蛋白，因此在肿瘤侵袭方面受到了广泛研究。现在人们逐渐认识到，基质金属蛋白酶在多种生物学过程中发挥着关键作用，这些作用与其在基质降解中明确的作用不同。已证明这组酶能与多种非基质蛋白相互作用，包括生长因子及其受体、凋亡介质和细胞黏附分子。对基质金属蛋白酶新生物学作用的阐明也对当前将基质金属蛋白酶仅视为参与基质降解的酶这一主流概念提出了挑战。最近的研究表明，几种基质金属蛋白酶，尤其是基质溶素（MMP - 7），与结直肠癌发生过程中涉及的特定分子遗传和信号通路相互作用。特别是，基质溶素在结直肠肿瘤发生的早期阶段被β - 连环蛋白信号通路激活。此外，目前的研究正在阐明单个基质金属蛋白酶，尤其是膜型基质金属蛋白酶，与特定细胞黏附分子和细胞骨架蛋白相互作用的具体机制，从而动态促进结直肠肿瘤侵袭。
