Pathological relevance of epithelial and mesenchymal phenotype plasticity

Epithelium and mesenchyme, two tissue types virtually found in every organ, are endowed with fundamentally different functional properties. Active motility, a capability that is limited to the mesenchymal repertoire, is the principal characteristic that distinguishes them. During embryonic development, conversions from epithelium to mesenchyme and from mesenchyme to epithelium normally occur, allowing morphogenetic processes and tissue remodelling to take place. However, there is now increasing evidence that the modulation between the epithelial and the mesenchymal phenotypes is not limited to embryonic life. Indeed, the pathogenesis of some adult diseases seems to implicate an inappropriate activation of this change. On the other hand, failure of normally occurring embryonic epithelial-mesenchymal interconversions could result in the development of some pathologies. It is now possible to study some molecular events underlying these phenotype transitions, since several biological agents implicated in the epithelial-mesenchymal interconversion, such as growth factors, extracellular matrix components and their receptors, transcription factors and oncogenes have been identified. The malignant potential of some oncogenes seems to express itself through the disruption of the mechanisms involved in the maintenance of the epithelial phenotype while, on the other hand, some observations suggest the existence of regulatory genes able to counteract the action of oncogenes by restoring epithelial characteristics. Therefore, the manipulation of the tissue phenotype could represent a novel strategy for the prevention and treatment of diseases in the future.