TY - JOUR
T1 - Extracellular vesicles secreted by triple-negative breast cancer stem cells trigger premetastatic niche remodeling and metastatic growth in the lungs
AU - González-Callejo, Patricia
AU - Gener, Petra
AU - Díaz Riascos, Zamira Vanessa
AU - Conti, Sefora
AU - Cámara-Sánchez, Patricia
AU - Riera Brillas, Roger
AU - Mancilla, Sandra
AU - García-Gabilondo, Miguel
AU - Peg, Vicente
AU - Arango, Diego
AU - Rosell Novel, Anna
AU - Labernadie, Anna
AU - Trepat, Xavier
AU - Albertazzi, Lorenzo
AU - Schwartz, S.
AU - Seras-Franzoso, Joaquin
AU - Abasolo, Ibane
PY - 2023
Y1 - 2023
N2 - 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; EVs and EVs, respectively) from the MDA-MB-231 TNBC cell line. Our results showed that EVs and EVs contain distinct bioactive cargos and therefore elicit a differential effect on stromal cells in the TME. Specifically, EVs activated secretory cancer associated fibroblasts (CAFs), triggering IL-6/IL-8 signaling and sustaining CSC phenotype maintenance. Complementarily, EVs 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 EVs mediated signaling prompted the transformation of healthy lungs into receptive niches able to support metastatic growth of breast cancer cells.
AB - 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; EVs and EVs, respectively) from the MDA-MB-231 TNBC cell line. Our results showed that EVs and EVs contain distinct bioactive cargos and therefore elicit a differential effect on stromal cells in the TME. Specifically, EVs activated secretory cancer associated fibroblasts (CAFs), triggering IL-6/IL-8 signaling and sustaining CSC phenotype maintenance. Complementarily, EVs 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 EVs mediated signaling prompted the transformation of healthy lungs into receptive niches able to support metastatic growth of breast cancer cells.
U2 - 10.1002/ijc.34447
DO - 10.1002/ijc.34447
M3 - Article
C2 - 36705298
SN - 0020-7136
VL - 152
SP - 2153
EP - 2165
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 10
ER -
