In contrast to epithelial cells, mesenchymal stem cells are multipotent stromal cells capable of differentiating into various cell types such as adipocytes, astrocytes, osteoblasts, chondrocytes, and myocytes.2,3 Mesenchymal cells appear elongated and spindle-shaped, and have loose cell-cell interaction in the absence of tight intracellular adhesion. As such, mesenchymal cells possess enhanced migratory capability as compared to epithelial cells.4
The ability of epithelial cells to downregulate their epithelial characteristics and acquire a mesenchymal phenotype was initially described in the 1980s.5 This phenomenon was originally terms "epithelial to mesenchymal transformation" but has since become known as "epithelial-mesenchymal transition" (EMT) in order to reflect the reversable nature of the process as well as to distinguish it from neoplastic transformation.6 The reverse process, involving the conversion of mesenchymal cells to epithelial derivatives, is called mesenchymal-epithelial transition (MET).7
An EMT is a biological process whereby the characteristically polarized epithelial cell, which would normally interact with basement membrane via its basal surface, undergoes multiple changes that result in adoption of a mesenchymal phenotype. These changes include a loss of characteristic apical-basal polarity and tight junctions, reorganization of the cytoskeleton, and a shift in cell shape. The result is enhanced migratory capacity, development of a more invasive phenotype, increased resistance to apoptosis, and vastly increased production of extracellular matrix components.7,8 The EMT is observed in both physiological and pathological processes, including embryogenesis and development, inflammation, wound healing, fibrosis, and tumor progression.9
A number of distinct processes are required to initiate and complete an EMT. These include transcription factor activation, expression of specific cell-surface proteins, a shift in the expression and organization of proteins comprising the cytoskeleton, production of enzymes which degrade the extracellular matrix, and changes in microRNA expression.10 It is these factors that can be used as biomarkers to indicate a cell undergoing EMT. For example, epithelial cells are typically indicated by markers such as E-cadherin, cytokeratin, zona occludens-1, and desmoplakin, among others. As the cell undergoes EMT, the expression of these markers wane, and that of mesenchymal markers such as fibroblast-specific protein-1, Smad interacting protein 1, fibronectin, and forkhead box C2, among others, increase.10 The end of the EMT is signaled by degradation of the underlying basement membrane and the formation of a mesenchymal cell that can migrate away from the epithelial layer in which it originated.
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