Cancer metastasis through the prism of epithelial-to-mesenchymal transition in circulating tumor cells

Abstract

Metastasis of epithelial cancer cells to distant sites is a particularly critical stage of cancer progression that typically marks the incurability of the disease. It is governed by a complex series of events including invasion and intravasation of tumor cells into the stroma and blood, respectively. Epithelial-to-mesenchymal transition (EMT), a phenotypic change marked by the loss of epithelial characteristics and the acquisition of invasive mesenchymal properties, is implicated in the dissemination of tumor cells. Circulating tumor cells (CTCs), the precursors of metastasis, can be used to interrogate the contribution of EMT in metastasis and therapeutic responses. The analysis of these CTCs and in particular the presence of inter- and intrapatient heterogeneity for markers of EMT has provided new insights into the metastatic process. This review will focus on epithelial-mesenchymal plasticity in CTCs and its potential clinical implications.

Keywords: cancer; circulating tumor cells; epithelial to mesenchymal transition; metastasis.

Figure 1

Epithelial‐to‐mesenchymal transition (EMT) in circulating tumor cells (CTCs): Invasive cells from the primary tumor exhibit epithelial plasticity including the loss of epithelial markers and gain of mesenchymal markers. Solitary and clusters of CTCs demonstrate heterogeneity of epithelial and mesenchymal markers.

Figure 2

Heterogeneity of CTCs in metastatic disease: CTCs represent the intrapatient tumor heterogeneity of cancer cells residing at multiple metastatic sites.