Professor Erik (Rik) Thompson, Head, Invasion and Metastasis Unit, St. Vincent's Institute and University of Melbourne Department of Surgery.
Epithelial-mesenchymal (EMT) and mesenchymal-epithelial (MET) transitions are important during normal development, in pathologic states such as fibrosis, and in carcinoma progression to metastases. Hybrid epithelial-mesenchymal states are seen in carcinoma cells, suggesting a continuum rather than a rigid set of transitions, or epithelial - mesenchymal plasticity (EMP). Mesenchymal features have been found to assist in local invasion and therapy resistance, while the epithelial collective is increasingly implicated in metastatic capability at distant sites, so PMC42-ET is a mesenchymal-like human breast cancer cell line from which the more epithelial PMC42-LA variant has been derived, providing a model of MET in which DNA methylation appears to play a major role. The PMC42 variants both respond to signals such as EGF, TGFβ and hypoxia with increased EMT, which is regulated at both the transcriptional and micro-RNA level. The MDA-MB-468 human breast cancer cell line also undergoes EMT in response to EGF and hypoxia in vitro, and while the PMC42 system in not amenable to study in murine hosts, MDA-MB-468 xenografts shows evidence of EMT in vivo at the stromal perimeter and at the necrotic interface. An apparent loss of epithelial features at the invasive front of MDA-MB-468 xenografts is reversed at metastatic sites, and even in lymphovascular emboli close to the tumour.
Understanding the regulators, mediators and stabilizers of these transitions may offer new diagnostic and therapeutic opportunities in cancer and other pathologies.