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Article

Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells

1
Laboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, Chile
2
Centro de Fisiología Celular e Integrativa, Facultad de Medicina, Universidad del Desarrollo, Santiago 7610658, Chile
3
Programa de Comunicación Celular en Cáncer, Instituto de Ciencias e Innovación en Medicina (ICIM), Santiago 7610658, Chile
4
Laboratory of Immunoncology, Fundación Ciencia & Vida, Santiago 7780272, Chile
5
Department of Obstetrics and Gynaecology, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, Chile
6
Cancer Cell Biology Lab, Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Lota 2465, Santiago 7510157, Chile
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(20), 4972; https://doi.org/10.3390/ijms20204972
Received: 16 September 2019 / Revised: 3 October 2019 / Accepted: 7 October 2019 / Published: 9 October 2019
Despite the different strategies used to treat ovarian cancer, around 70% of women/patients eventually fail to respond to the therapy. Cancer stem cells (CSCs) play a role in the treatment failure due to their chemoresistant properties. This capacity to resist chemotherapy allows CSCs to interact with different components of the tumor microenvironment, such as mesenchymal stem cells (MSCs), and thus contribute to tumorigenic processes. Although the participation of MSCs in tumor progression is well understood, it remains unclear how CSCs induce the pro-tumorigenic activity of MSCs in response to chemotherapy. Small extracellular vesicles, including exosomes, represent one possible way to modulate any type of cell. Therefore, in this study, we evaluate if small extracellular vesicle (sEV) derived from ovarian cancer spheroids (OCS), which are enriched in CSCs, can modify the activity of MSCs to a pro-tumorigenic phenotype. We show that sEV released by OCS in response to cisplatin induce an increase in the migration pattern of bone marrow MSCs (BM-MSCs) and the secretion interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor A (VEGFA). Moreover, the factors secreted by BM-MSCs induce angiogenesis in endothelial cells and the migration of low-invasive ovarian cancer cells. These findings suggest that cisplatin could modulate the cargo of sEV released by CSCs, and these exosomes can further induce the pro-tumorigenic activity of MSCs. View Full-Text
Keywords: small extracellular vesicles; cancer stem cells; spheroids; cisplatin; tumor microenvironment; bone marrow mesenchymal stem cells small extracellular vesicles; cancer stem cells; spheroids; cisplatin; tumor microenvironment; bone marrow mesenchymal stem cells
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MDPI and ACS Style

Vera, N.; Acuña-Gallardo, S.; Grünenwald, F.; Caceres-Verschae, A.; Realini, O.; Acuña, R.; Lladser, A.; Illanes, S.E.; Varas-Godoy, M. Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells. Int. J. Mol. Sci. 2019, 20, 4972. https://doi.org/10.3390/ijms20204972

AMA Style

Vera N, Acuña-Gallardo S, Grünenwald F, Caceres-Verschae A, Realini O, Acuña R, Lladser A, Illanes SE, Varas-Godoy M. Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells. International Journal of Molecular Sciences. 2019; 20(20):4972. https://doi.org/10.3390/ijms20204972

Chicago/Turabian Style

Vera, Nelly, Stephanie Acuña-Gallardo, Felipe Grünenwald, Albano Caceres-Verschae, Ornella Realini, Rodrigo Acuña, Alvaro Lladser, Sebastián E. Illanes, and Manuel Varas-Godoy. 2019. "Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells" International Journal of Molecular Sciences 20, no. 20: 4972. https://doi.org/10.3390/ijms20204972

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