RT Journal Article
T1 Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
A1 Abreu Rodríguez, Manuel
A1 Cabezas Sáinz, Pablo
A1 Pereira Veiga, Tais
A1 Falo, Catalina
A1 Abalo, Alicia
A1 Morilla, Idoia
A1 Curiel, Teresa
A1 Cueva, Juan
A1 Rodríguez, Carmela
A1 Varela Pose, Vanesa
A1 Lago Lestón, Ramón
A1 Mondelo, Patricia
A1 Palacios, Patricia
A1 Moreno Bueno, Gema
A1 Cano, Amparo
A1 García-Caballero Parada, Tomás
A1 Pujana, Miguel Ángel
A1 Sánchez Piñón, Laura
A1 Costa, Clotilde
A1 López López, Rafael
A1 Muinelo Romay, Laura
K1 Triple-Negative Breast Cancer (Tnbc)
K1 Circulating Tumor Cells (Ctcs)
K1 Metastasis
K1 Cell Plasticity
K1 Epithelial To Mesenchymal Transition
K1 Stemness
K1 Tumor Biomarkers
K1 Tissue Inhibitor Of Metalloproteinases 1
K1 Androgen Receptor
K1 Therapeutic Targets
AB 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.
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/21782
UL http://hdl.handle.net/10347/21782
LA eng
NO 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.
NO This work was supported by grants from the Instituto de Salud Carlos III (ISCIII) and FEDER (PI13/01388 to RL, CB16/12/00328 to RL, LM and CC, PI16/00134 to GMB and CB16/12/00295 CIBERONC to AC and GMB. This research was also funded by Roche-Chus Joint Unit (IN853B 2018/03) funded by GAIN, Consellería de Economía, Emprego e Industria. LMR is nowadays supported by AECC
DS Minerva
RD 25 abr 2026