Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
Abreu, M.; Cabezas-Sainz, P.; Pereira Veiga, Thais; Falo, C.; Abalo, A.; Morilla, I.; Curiel Garcïa, Teresa; Cueva Bañuelos, Juan Fernando; Rodríguez López, Carmela; VARELA POSE, VANESA; Lago-Leston, R.; Mondelo, P.; Palacios Ozores, Patricia; Moreno-Bueno, G.; Cano, A.; García-Caballero Parada, Tomas; Pujana, M. A.; Sanchez-Pinon, L.; Costa Nogueira, Clotilde; López López, Rafael; Muinelo-Romay, L.
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Identificadores![](/xmlui/themes/Mirage2//images/despl_identif.png)
Identificadores
URI: http://hdl.handle.net/20.500.11940/16583
PMID: 32012729
DOI: 10.3390/jcm9020353
ISSN: 2077-0383
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Fecha de publicación
2020Título de revista
Journal of Clinical Medicine
Tipo de contenido
Journal Article
Resumen
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.
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