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

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...

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Autores principales: Abreu, Manuel, Cabezas-Sainz, Pablo, Pereira-Veiga, Thais, Falo, Catalina, Abalo, Alicia, Morilla, Idoia, Curiel, Teresa, Cueva, Juan, Rodríguez, Carmela, Varela-Pose, Vanesa, Lago-Lestón, Ramón, Mondelo, Patricia, Palacios, Patricia, Moreno-Bueno, Gema, Cano, Amparo, García-Caballero, Tomás, Pujana, Miquel Ángel, Sánchez-Piñón, Laura, Costa, Clotilde, López, Rafael, Muinelo-Romay, Laura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074553/
https://www.ncbi.nlm.nih.gov/pubmed/32012729
http://dx.doi.org/10.3390/jcm9020353
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author Abreu, Manuel
Cabezas-Sainz, Pablo
Pereira-Veiga, Thais
Falo, Catalina
Abalo, Alicia
Morilla, Idoia
Curiel, Teresa
Cueva, Juan
Rodríguez, Carmela
Varela-Pose, Vanesa
Lago-Lestón, Ramón
Mondelo, Patricia
Palacios, Patricia
Moreno-Bueno, Gema
Cano, Amparo
García-Caballero, Tomás
Pujana, Miquel Ángel
Sánchez-Piñón, Laura
Costa, Clotilde
López, Rafael
Muinelo-Romay, Laura
author_facet Abreu, Manuel
Cabezas-Sainz, Pablo
Pereira-Veiga, Thais
Falo, Catalina
Abalo, Alicia
Morilla, Idoia
Curiel, Teresa
Cueva, Juan
Rodríguez, Carmela
Varela-Pose, Vanesa
Lago-Lestón, Ramón
Mondelo, Patricia
Palacios, Patricia
Moreno-Bueno, Gema
Cano, Amparo
García-Caballero, Tomás
Pujana, Miquel Ángel
Sánchez-Piñón, Laura
Costa, Clotilde
López, Rafael
Muinelo-Romay, Laura
author_sort Abreu, Manuel
collection PubMed
description 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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spelling pubmed-70745532020-03-20 Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells Abreu, Manuel Cabezas-Sainz, Pablo Pereira-Veiga, Thais Falo, Catalina Abalo, Alicia Morilla, Idoia Curiel, Teresa Cueva, Juan Rodríguez, Carmela Varela-Pose, Vanesa Lago-Lestón, Ramón Mondelo, Patricia Palacios, Patricia Moreno-Bueno, Gema Cano, Amparo García-Caballero, Tomás Pujana, Miquel Ángel Sánchez-Piñón, Laura Costa, Clotilde López, Rafael Muinelo-Romay, Laura J Clin Med Article 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. MDPI 2020-01-27 /pmc/articles/PMC7074553/ /pubmed/32012729 http://dx.doi.org/10.3390/jcm9020353 Text en © 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/).
spellingShingle Article
Abreu, Manuel
Cabezas-Sainz, Pablo
Pereira-Veiga, Thais
Falo, Catalina
Abalo, Alicia
Morilla, Idoia
Curiel, Teresa
Cueva, Juan
Rodríguez, Carmela
Varela-Pose, Vanesa
Lago-Lestón, Ramón
Mondelo, Patricia
Palacios, Patricia
Moreno-Bueno, Gema
Cano, Amparo
García-Caballero, Tomás
Pujana, Miquel Ángel
Sánchez-Piñón, Laura
Costa, Clotilde
López, Rafael
Muinelo-Romay, Laura
Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
title Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
title_full Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
title_fullStr Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
title_full_unstemmed Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
title_short Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells
title_sort looking for a better characterization of triple-negative breast cancer by means of circulating tumor cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074553/
https://www.ncbi.nlm.nih.gov/pubmed/32012729
http://dx.doi.org/10.3390/jcm9020353
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