Extracellular vesicles secreted by triple-negative breast cancer stem cells trigger premetastatic niche remodeling and metastatic growth in the lungs
| Autor: | Patricia González‐Callejo, Petra Gener, Zamira V. Díaz‐Riascos, Sefora Conti, Patricia Cámara‐Sánchez, Roger Riera, Sandra Mancilla, Miguel García‐Gabilondo, Vicente Peg, Diego Arango, Anna Rosell, Anna Labernadie, Xavier Trepat, Lorenzo Albertazzi, Simó Schwartz, Joaquin Seras‐Franzoso, Ibane Abasolo |
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| Přispěvatelé: | Immunoengineering, Molecular Biosensing for Med. Diagnostics, Nanoscopy for Nanomedicine, ICMS Core |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: |
Cancer Research
Cancer cells Pulmó premetastatic niche Stem cells SDG 3 – Goede gezondheid en welzijn Càncer de mama Metastasis Breast cancer Metàstasi Oncology SDG 3 - Good Health and Well-being Neuroplasticitat triple-negative breast cancer tumor microenvironment Cèl·lules canceroses Neuroplasticity Extracellular space cancer cell plasticity Espai extracel·lular Cèl·lules mare extracellular vesicles Lung |
| Zdroj: | International Journal of Cancer, 152(10), 2153-2165. Wiley-Liss Inc. |
| ISSN: | 0020-7136 |
| Popis: | Tumor secreted extracellular vesicles (EVs) are potent intercellular signaling platforms. They are responsible for the accommodation of the premetastatic niche (PMN) to support cancer cell engraftment and metastatic growth. However, complex cancer cell composition within the tumor increases also the heterogeneity among cancer secreted EVs subsets, a functional diversity that has been poorly explored. This phenomenon is particularly relevant in highly plastic and heterogenous triple-negative breast cancer (TNBC), in which a significant representation of malignant cancer stem cells (CSCs) is displayed. Herein, we selectively isolated and characterized EVs from CSC or differentiated cancer cells (DCC; EVsCSC and EVsDCC, respectively) from the MDA-MB-231 TNBC cell line. Our results showed that EVsCSC and EVsDCC contain distinct bioactive cargos and therefore elicit a differential effect on stromal cells in the TME. Specifically, EVsDCC activated secretory cancer associated fibroblasts (CAFs), triggering IL-6/IL-8 signaling and sustaining CSC phenotype maintenance. Complementarily, EVsCSC promoted the activation of α-SMA+ myofibroblastic CAFs subpopulations and increased the endothelial remodeling, enhancing the invasive potential of TNBC cells in vitro and in vivo. In addition, solely the EVsCSC mediated signaling prompted the transformation of healthy lungs into receptive niches able to support metastatic growth of breast cancer cells. |
| Databáze: | OpenAIRE |
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