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Open AccessArticle

Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells

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Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain
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Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Campus de Lugo, 27002 Lugo, Spain
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Roche-CHUS Joint Unit, Oncomet, Health Research Institute of Santiago (IDIS), Complejo Hospitalario de Santiago de Compostela, Trav. Choupana s/n, 15706 Santiago de Compostela, Spain
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Department of Medical Oncology-Breast Cancer Unit, Institut Català d’Oncologia (ICO)-Hospitalet-Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Universitat de Barcelona, 08007 Barcelona, Spain
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Translational Medical Oncology (Oncomet), Health Research Institute of Santiago de Compostela (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), 15706 Santiago de Compostela, Spain
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Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Monforte de Lemos 3-5, 28029 Madrid, Spain
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Fundación MD Anderson Internacional, C/Gómez Hemans 2, 28033 Madrid, Spain
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Departamento de Bioquímica, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas ‘Alberto Sols’ (CSIC-UAM), IdiPaz, Arzobispo Morcillo 4, 28029 Madrid, Spain
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Departamento de Ciencias Morfológicas, Facultad de Medicina, Universidad de Santiago, Servicio de Anatomía Patológica, Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain
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ProCURE, Catalan Institute of Oncology (ICO), Bellvitge Institute of Biomedical Research (IDIBELL), 08908 Barcelona, Spain
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2020, 9(2), 353; https://doi.org/10.3390/jcm9020353
Received: 7 January 2020 / Revised: 17 January 2020 / Accepted: 21 January 2020 / Published: 27 January 2020
(This article belongs to the Special Issue Circulating Biomarkers as a Liquid Biopsy for Cancer)
Traditionally, studies to address the characterization of mechanisms promoting tumor aggressiveness and progression have been focused only on primary tumor analyses, which could provide relevant information but have limitations to really characterize the more aggressive tumor population. To overcome these limitations, circulating tumor cells (CTCs) represent a noninvasive and valuable tool for real-time profiling of disseminated tumor cells. Therefore, the aim of the present study was to explore the value of CTC enumeration and characterization to identify markers associated with the outcome and the aggressiveness of triple-negative breast cancer (TNBC). For that aim, the CTC population from 32 patients diagnosed with TNBC was isolated and characterized. This population showed important cell plasticity in terms of expression of epithelia/mesenchymal and stemness markers, suggesting the relevance of epithelial to mesenchymal transition (EMT) intermediate phenotypes for efficient tumor dissemination. Importantly, the CTC signature demonstrated prognostic value to predict the patients’ outcome and pointed to a relevant role of tissue inhibitor of metalloproteinases 1 (TIMP1) and androgen receptor (AR) for TNBC biology. Furthermore, we also analyzed the usefulness of the AR and TIMP1 blockade to target TNBC proliferation and dissemination using in vitro and in vivo zebra fish and mouse models. Overall, the molecular characterization of CTCs from advanced TNBC patients identifies highly specific biomarkers with potential applicability as noninvasive prognostic markers and reinforced the value of TIMP1 and AR as potential therapeutic targets to tackle the most aggressive breast cancer.
Keywords: triple-negative breast cancer (TNBC); circulating tumor cells (CTCs); metastasis; cell plasticity; epithelial to mesenchymal transition; stemness; tumor biomarkers; tissue inhibitor of metalloproteinases 1; androgen receptor; therapeutic targets triple-negative breast cancer (TNBC); circulating tumor cells (CTCs); metastasis; cell plasticity; epithelial to mesenchymal transition; stemness; tumor biomarkers; tissue inhibitor of metalloproteinases 1; androgen receptor; therapeutic targets
MDPI and ACS Style

Abreu, M.; Cabezas-Sainz, P.; Pereira-Veiga, T.; Falo, C.; Abalo, A.; Morilla, I.; Curiel, T.; Cueva, J.; Rodríguez, C.; Varela-Pose, V.; Lago-Lestón, R.; Mondelo, P.; Palacios, P.; Moreno-Bueno, G.; Cano, A.; García-Caballero, T.; Pujana, M.Á.; Sánchez-Piñón, L.; Costa, C.; López, R.; Muinelo-Romay, L. Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells. J. Clin. Med. 2020, 9, 353.

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