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 mot ility, a capability that is limited to the mesenchymal repertoire, is the p rincipal characteristic that distinguishes them. During embryonic developme nt, conversions from epithelium to mesenchyme and from mesenchyme to epithe lium normally occur, allowing morphogenetic processes and tissue remodellin g to take place. However, there is now increasing evidence that the modulat ion between the epithelial and the mesenchymal phenotypes is not limited to embryonic life. Indeed, the pathogenesis of some adult diseases seems to i mplicate an inappropriate activation of this change. On the other hand, fai lure of normally occurring embryonic epithelial-mesenchymal interconversion s could result in the development of some pathologies. It is now possible t o study some molecular events underlying these phenotype transitions, since several biological agents implicated in the epithelial-mesenchymal interco nversion, such as growth factors, extracellular matrix components and their receptors, transcription factors and oncogenes have been identified. The m alignant potential of some oncogenes seems to express itself through the di sruption of the mechanisms involved in the maintenance of the epithelial ph enotype while, on the other hand, some observations suggest the existence o f regulatory genes able to counteract the action of oncogenes by restoring epithelial characteristics. Therefore, the manipulation of the tissue pheno type could represent a novel strategy for the prevention and treatment of d iseases in the future.