EMT, MET, Plasticity, and Tumor Metastasis

Abstract

Cancer cell identity and plasticity are required in transition states, such as epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET), in primary tumor initiation, progression, and metastasis. The functional roles of EMT, MET, and the partial state (referred to as pEMT) may vary based on the type of tumor, the state of dissemination, and the degree of metastatic colonization. Herein, we review EMT, MET, pEMT, and plasticity in the context of tumor metastasis.

Keywords: EMT; MET; cellular plasticity; colonization; metastasis; pEMT.

Figure 1:. Primary tumor cells undergo intravasation into the lymphatic-vascular systems.

There are multiple mechanisms by which tumor cells (blue rectangles) are thought to detach from the primary site and intravasate into the lymphatic-vascular systems. One proposed mechanism is complete EMT or cEMT (green spheres), whereby cells lose epithelial markers and gain mesenchymal characteristics. During partial EMT or pEMT, cells retain some of their epithelial characteristics. Another possibility is that cells undergoing EMT represent only a small portion of the total population that ultimately metastasize.

Figure 2:. Primary tumor cells undergo extravasation and metastatic colonization.

Evidence in multiple model systems demonstrates that macrometastases have strong expression of epithelial markers (blue), which are likely a requirement for expansion within the metastatic site. One model suggests cells that previously underwent cEMT or pEMT regain epithelial markers and lose mesenchymal characteristics (green). Lastly, in mixed populations of metastatic cells, it is thought that the clusters of epithelial cells are the exclusive or dominant population capable of expanding and forming macrometastases.