Epithelial-to-mesenchymal change of differentiation. From embryogenetic mechanism to pathological patterns

Abstract

In embryonic morphogenesis, dramatic changes from one state of differentiation to another take place, and some epithelia transform into mesenchymal cells endowed with the ability to migrate and to form connective tissue. In vitro model systems have been developed which have provided new insights into crucial aspects of this differentiation change. Triggered perhaps by either extracellular matrix or growth factors, this phenotypic conversion involves a reorganization of the cytoskeleton, and changes in both cell-cell and cell-matrix interactions. As embryonic and adult tissues contain the same, albeit differently expressed, genetic information, one could expect, under particular circumstances, conversion to mesenchyme from epithelium to occur in adult tissues too. Indeed, there is evidence that this change really occurs in human diseases: some tissue reactions to injury; the process of tumour invasion and metastasis; and the development of carcinosarcomas, are all pathological conditions in which an epithelial conversion into mesenchyme probably plays a role. Here, recent observations on embryonic and in vitro epithelial-mesenchymal conversion are reviewed, and these data are compared with findings from some pathological situations. Many similarities emerge which further strengthen the belief that this change in differentiation is involved in the pathogenesis, and underlies the pathological pattern of some diseases.