Heterogeneity in circulating tumor cells : the relevance of the stem-cell subset

Agnoletto, C ORCID: https://orcid.org/0000-0002-1363-5852, Corrà, F, Minotti, L ORCID: https://orcid.org/0000-0003-2116-8411, Baldassari, F, Crudele, F ORCID: https://orcid.org/0000-0003-4638-9122, Cook, WJJ ORCID: https://orcid.org/0000-0003-3735-6134, Di Leva, G ORCID: https://orcid.org/0000-0002-7656-510X, d’Adamo, AP ORCID: https://orcid.org/0000-0001-9367-4909, Gasparini, P and Volinia, S 2019, 'Heterogeneity in circulating tumor cells : the relevance of the stem-cell subset' , Cancers, 11 (4) , e483.

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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.

Item Type:	Article
Schools:	Schools > School of Environment and Life Sciences
Journal or Publication Title:	Cancers
Publisher:	MDPI
ISSN:	2072-6694
Related URLs:	Publisher
Funders:	Associazione Italiana Ricerca sul Cancro AIRC
SWORD Depositor:	Publications Router
Depositing User:	Publications Router
Date Deposited:	09 Apr 2019 08:52
Last Modified:	16 Feb 2022 01:37
URI:	https://usir.salford.ac.uk/id/eprint/51005

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