Abreu Rodríguez, ManuelCabezas Sáinz, PabloPereira Veiga, TaisFalo, CatalinaAbalo, AliciaMorilla, IdoiaCuriel, TeresaCueva, JuanRodríguez, CarmelaVarela Pose, VanesaLago Lestón, RamónMondelo, PatriciaPalacios, PatriciaMoreno Bueno, GemaCano, AmparoGarcía-Caballero Parada, TomásPujana, Miguel ÁngelSánchez Piñón, LauraCosta, ClotildeLópez López, RafaelMuinelo Romay, Laura2020-04-272020-04-272020Abreu, 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.http://hdl.handle.net/10347/21782Traditionally, 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.eng© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)https://creativecommons.org/licenses/by/4.0/Triple-Negative Breast Cancer (Tnbc)Circulating Tumor Cells (Ctcs)MetastasisCell PlasticityEpithelial To Mesenchymal TransitionStemnessTumor BiomarkersTissue Inhibitor Of Metalloproteinases 1Androgen ReceptorTherapeutic Targetsjournal article10.3390/jcm90203532077-0383open access