Genesis of Circulating Tumor Cells Through Epithelial–Mesenchymal Transition as a Mechanism for Distant Dissemination

Epithelial–mesenchymal transition (EMT), a developmental process through which epithelial cells lose their characteristic apicobasal polarity and acquire the morphology of solitary migratory cells, has been implicated in the progression of carcinoma. EMT may contribute to the formation of cancer stem cells, evasion of immune surveillance, and induction of resistance to chemotherapeutics and targeted therapeutics. Metastasis is governed by a complex set of processes that are far from being fully understood and difficult to recapitulate through the current suite of in vitro experimentations. Circulating tumor cells (CTCs) in the peripheral blood have received much attention recently, as they may represent the first critical stage of cancer dissemination and their prevalence in metastatic patients is associated with worse prognosis. CTCs exhibit significant phenotypic heterogeneity across the EMT spectrum and preliminary studies have prompted the need to unravel the mechanisms by which CTCs are generated and how this diversity is attained in primary tumors. As such, improved methodologies are required to exhaustively characterize the full spectrum of CTC phenotypes and to identify the clonogenic cells. An understanding of the EMT phenotypes in CTCs should help in the design of more appropriate targeted therapeutics to abrogate the malignant potential of CTCs.