Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles vaeg 2, 17177 Stockholm, Sweden.
Eur J Cell Biol. 2016 Nov;95(11):427-440. doi: 10.1016/j.ejcb.2016.06.002. Epub 2016 Jun 18.
The epithelial-to-mesenchymal transition (EMT) enables cells of epithelial phenotype to become motile and change to a migratory mesenchymal phenotype. EMT is known to be a fundamental requisite for tissue morphogenesis, and EMT-related pathways have been described in cancer metastasis and tissue fibrosis. Epithelial structures are marked by the presence of a sheet-like extracellular matrix, the basement membrane, which is assembled from two major proteins, laminin and collagen type IV. This specialized matrix is essential for tissue function and integrity, and provides an important barrier to the potential pathogenic migration of cells. The profound phenotypic transition in EMT involves the epithelial cells disrupting the basement membrane. Matrix metalloproteinases (MMPs) are known to cleave components of basement membranes, but MMP-basement membrane crosstalk during EMT in vivo is poorly understood. However, MMPs have been reported to play a role in EMT-related processes and a variety of basement membrane fragments have been shown to be released by specific MMPs in vitro and in vivo exhibiting distinct biological activities. This review discusses general considerations regarding the basement membrane in the context of EMT, a possible role for specific MMPs in EMT and highlights biologically active basement membrane fragments liberated by MMPs.
上皮-间充质转化（EMT）使上皮表型的细胞能够变得运动并转变为迁移的间充质表型。EMT 已知是组织形态发生的基本要求，并且在癌症转移和组织纤维化中已经描述了与 EMT 相关的途径。上皮结构的特征是存在片状细胞外基质，即基底膜，它由两种主要蛋白质，层粘连蛋白和 IV 型胶原组成。这种特殊的基质对于组织功能和完整性至关重要，并为细胞的潜在致病迁移提供了重要的屏障。EMT 中深刻的表型转变涉及上皮细胞破坏基底膜。基质金属蛋白酶（MMPs）已知可切割基底膜的成分，但体内 EMT 期间 MMP-基底膜相互作用知之甚少。然而，据报道 MMPs 在 EMT 相关过程中发挥作用，并且已经显示特定 MMP 在体外和体内释放多种具有不同生物学活性的基底膜片段。这篇综述讨论了 EMT 背景下基底膜的一般考虑因素、特定 MMP 在 EMT 中的可能作用以及 MMP 释放的具有生物活性的基底膜片段。
