Basement membrane fragments in the context of the epithelial-to-mesenchymal transition

Abstract

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.