Implications of Mesenchymal Cells in Cancer Stem Cell Populations: Relevance to EMT

Abstract

The epithelial to mesenchymal transition (EMT) generates tumor cells with stem cell characteristics and with phenotypes similar to those of cancer stem cells (CSCs). Evidence suggests CSCs are in an intermediate state of EMT expressing reduced levels of E-cadherin and with mesenchymal features including invasiveness associated with metastasis. These findings suggest mechanisms regulating EMT and stemness are closely integrated. Recent reports from several laboratories have identified novel mechanisms regulating EMT and stemness involving epigenetics, microenvironment, and dedifferentiation. Circulating tumor cells (CTCs) have also been shown to have features of EMT, but it is unclear which fraction has the properties of CSCs. EMT characteristics of both CSCs and CTCs are associated with resistance to current clinical treatments, indicating that therapy targeting CSCs in addition to more differentiated tumor cells are required for durable responses. Thus, EMT characteristics of CTCs may prove useful biomarkers for effective therapy for many cancers.