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Cancers 2019, 11(4), 483; https://doi.org/10.3390/cancers11040483

Heterogeneity in Circulating Tumor Cells: The Relevance of the Stem-Cell Subset

1
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy
2
School of Environment and Life Sciences, University of Salford, Salford M5 4WT, UK
3
Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy
4
Institute for Maternal and Child Health—IRCCS “Burlo Garofolo”, 34137 Trieste, Italy
*
Author to whom correspondence should be addressed.
Received: 1 February 2019 / Revised: 16 March 2019 / Accepted: 30 March 2019 / Published: 5 April 2019
(This article belongs to the Special Issue Advances in Cancer Stem Cell Research)
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Abstract

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process. The analysis of CTCs in patients has recently received widespread attention because of its clinical implications, particularly for precision medicine. Accumulated evidence documents a large heterogeneity in CTCs across patients. Currently, the most accepted view is that tumor cells with an intermediate phenotype between epithelial and mesenchymal have the highest plasticity. Indeed, the existence of a meta-stable or partial epithelial–mesenchymal transition (EMT) cell state, with both epithelial and mesenchymal features, can be easily reconciled with the concept of a highly plastic stem-like state. A close connection between EMT and cancer stem cells (CSC) traits, with enhanced metastatic competence and drug resistance, has also been described. Accordingly, a subset of CTCs consisting of CSC, present a stemness profile, are able to survive chemotherapy, and generate metastases after xenotransplantation in immunodeficient mice. In the present review, we discuss the current evidence connecting CTCs, EMT, and stemness. An improved understanding of the CTC/EMT/CSC connections may uncover novel therapeutic targets, irrespective of the tumor type, since most cancers seem to harbor a pool of CSCs, and disclose important mechanisms underlying tumorigenicity. View Full-Text
Keywords: CTC; EMT; stemness; CSC CTC; EMT; stemness; CSC
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Agnoletto, C.; Corrà, F.; Minotti, L.; Baldassari, F.; Crudele, F.; Cook, W.J.J.; Di Leva, G.; d’Adamo, A.P.; Gasparini, P.; Volinia, S. Heterogeneity in Circulating Tumor Cells: The Relevance of the Stem-Cell Subset. Cancers 2019, 11, 483.

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