Epithelial-mesenchymal transition and tumour invasion.
Carcinoma invasion implies potentiality to metastasize distantly but, despite its clinical importance, it is still a poorly understood process. There is increasing evidence pointing to a role of epithelial-mesenchymal transition by which tumour cells would weaken E-cadherin-dependent intercellular adhesion and enhance motility, thus becoming able to penetrate into surrounding tissues. The activated tissue microenvironment at the advancing tumour front seems to provide the appropriate stimuli for triggering this change. The binding of growth factors and extracellular matrix molecules to tumour cell membrane receptors generates cascades of intracellular signals that could ultimately promote the down-regulation of E-cadherin and the activation of the cytoskeleton. Therefore, cells lose intercellular junctions and emanate cytoplasmic extensions that protrude from the basal surface into the stromal compartment through interruptions of the basement membrane. These protrusions establish new contacts with the interstitial matrix and, finally, the contraction of the cytoskeleton allows cell translocation into the stroma. Here, repeated cycles of spatially and temporally coordinated protrusive and contractile events ensure the locomotion of invading cells. Invasion predicts the ability to generate metastasis, therefore epithelial-mesenchymal transition could provide new insights on the mechanisms underlying this detrimental process. Furthermore, since deregulated proteins known to be involved in epithelial-mesenchymal transition seem associated with cancer progression, they could potentially be utilized as prognostic markers or therapeutic targets. Thus, in addition to increasing our knowledge of tumour invasion biology, studying epithelial-mesenchymal transition will, in the future, offer novel opportunities to define clinical parameters and pharmacological treatment.
Guarino
Marcello
M
Department of Anatomical Pathology, Hospital of Vimercate, via C. Battisti 23, 20059 Vimercate (MI), Italy. guarino.marcello@alice.it
D000818:Animals; D002465:Cell Movement / Q000502:physiology; D004848:Epithelium / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008648:Mesoderm / Q000473:pathology*; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D020741:rho GTP-Binding Proteins / Q000378:metabolism