EPITHELIAL-MESENCHYMAL TRANSITIONS (EMT)
 R.A.S HEMAT, MB;BCh, FRCSI, Dip.Urol.UCL.
Epithelia form continuous sheets of tightly adhering cells. Polar epithelial cells have evolved special mechanisms that allow the transport of membrane proteins to either the apical or basolateral surface.
E-cadherin is the prototype of a family of Ca2+-dependent cell adhesion molecules, close relatives are N-cadherin (neurones) and P-cadherin (placenta and epithelia), M-cadherin (muscle), OB-cadherin (osteoblasts), and LI-cadherin (liver). The integrity of this junctional complex is critical for the maintenance of the functional characteristics of epithelia. Its disruption leads to the dissociation of epithelial sheets, a change in cell morphology to a more flattened shape, and to an increased motility of the cells.
The basement membrane separates the epithelial cell compartment from underlying mesenchymal cells and is formed by both cell types. The epithelial receptors for basement membrane components are located on the basal surface of the plasma membrane.
Mesenchymal cells in contrast to epithelial cells are generally loosely associated, and are surrounded by extracellular matrix (ECM). Mesenchymal cells also express specific ligands for various epithelial receptor tyrosine kinases, such as HGF or KGF, and thereby play an important role in the control of epithelial growth, morphogenesis and differentiation.
E-cadherin is important for maintenance of morphology and adhesion in differentiated epithelia and also for the acquisition of epithelial characteristics early in embryogenesis. The integrity of the adherens junction also requires functional catinen molecules. Morphogenesis requires an intact epithelial program, whereas metastatic behaviour is observed in cells that have already undergone EMT.
Various molecular mechanisms can interfere with the integrity of the adherens junction and can induce epithelial cells to assume mesenchymal characteristics, which correlates with dedifferentiation of the cells and increased metastatic potential. In human carcinoma, the loss of epithelial morphology is an important prognostic marker and correlates with a poor outcome of the disease. The invading cells can lose their epithelial appearance, become spindle-shaped and fibroblast-like with reduced number of desmosomes. Carcinoma cells with a well-differentiated epithelial morphology do not invade a collagen matrix, and produce E-cadherin. Loss of epithelial morphology and the acquisition of mesenchymal characteristics are typical for carcinoma cells late in tumour progression and correlate with metastatic potential. In carcinoma, downregulation of E-cadherin correlates with poor survival rates.
During gastrulation the three germinal layers, namely the embryonic endoderm, the embryonic mesoderm and the embryonic ectoderm, develop from the primitive ectoderm. Whereas the former two layers keep their epithelial phenotype, epithelial-mesenchymal transition (EMT) leads to the development of the first mesoderm. In EMT, epithelial cells become elongated and mobile and lose their polarity and firm cellular junctions.
The transformation event from a nonmalignant to a malignant mimics the losses of polarisation, motility, and cellular contacts that occur during EMT.
January, 2005
Note: The information in this article has been excerpted from the following books: urotext-ebook simplifying urology (urotext-Basics volume 1), Principles of modern urology, by Dr. R.A.S HEMAT. Permission is granted to copy and redistribute this document electronically as long as it is unmodified. This article may not be sold in any medium, including electronic, CD-ROM, or database, or published in print, without the explicit, written permission of Dr. R. A. S. Hemat.
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Dr. R.A.S HEMAT declares no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, stock holdings, gifts, or honoraria.
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