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

Journal of Clinical Medicine

Amparo Cano¹  Gema Moreno-Bueno¹  Tomás García-Caballero²  Catalina Falo³  Idoia Morilla³  Pablo Cabezas-Sainz⁴  Laura Sánchez-Piñón⁴  Manuel Abreu⁵  Patricia Mondelo⁵  Ramón Lago-Lestón⁵  Laura Muinelo-Romay⁵  Alicia Abalo⁵  Rafael López⁵  MiquelÁngel Pujana⁶  Thais Pereira-Veiga⁷  Clotilde Costa⁷  Vanesa Varela-Pose⁸  Teresa Curiel⁸  Juan Cueva⁸  Patricia Palacios⁸  Carmela Rodríguez⁸ 

[1] Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Monforte de Lemos 3-5, 28029 Madrid, Spain;Departamento de Ciencias Morfológicas, Facultad de Medicina, Universidad de Santiago, Servicio de Anatomía Patológica, Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain;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;Department of Zoology, Genetics and Physical Anthropology, Universidade de Santiago de Compostela, Campus de Lugo, 27002 Lugo, Spain;Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain;ProCURE, Catalan Institute of Oncology (ICO), Bellvitge Institute of Biomedical Research (IDIBELL), 08908 Barcelona, Spain;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;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;

关键词: 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;   

DOI  :  10.3390/jcm9020353

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown