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

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dc.contributor.authorVera, Nelly
dc.contributor.authorAcuña-Gallardo, Stephanie
dc.contributor.authorGrünenwald, Felipe
dc.contributor.authorCáceres-Verschae, Albano
dc.contributor.authorRealini, Ornela
dc.contributor.authorAcuña, Rodrigo
dc.contributor.authorLladser, Álvaro
dc.contributor.authorIllanes, Sebastián
dc.contributor.authorVaras-Godoy, Manuel
dc.date.accessioned2020-03-09T13:53:26Z
dc.date.available2020-03-09T13:53:26Z
dc.date.issued2019
dc.descriptionPrograma de Comunicación Celular en Cáncer (ICIM),
dc.description.abstractDespite 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.
dc.identifier.citationInt J Mol Sci. 2019 Oct 9;20(20). pii: E4972. doi: 10.3390/ijms20204972.
dc.identifier.urihttp://hdl.handle.net/11447/3121
dc.identifier.urihttps://doi.org/10.3390/ijms20204972
dc.language.isoen
dc.publisherMDPI
dc.subjectBone marrow mesenchymal stem cells
dc.subjectCancer stem cells
dc.subjectCisplatin
dc.subjectSmall extracellular vesicles
dc.subjectSpheroids
dc.subjectTumor microenvironment
dc.titleSmall Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells
dc.typeArticle

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