Small extracellular vesicles released from ovarian cancer spheroids in response to cisplatin promote the pro-tumorigenic activity of mesenchymal stem cells

Nelly Vera, Stephanie Acuña-Gallardo, Felipe Grünenwald, Albano Caceres-Verschae, Ornella Realini, Rodrigo Acuña, Alvaro Lladser, Sebastián Illanes, Manuel Varas-Godoy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish
Article number4972
JournalInternational Journal of Molecular Sciences
Volume20
Issue number20
DOIs
StatePublished - 2 Oct 2019

Bibliographical note

Funding Information:
Funding: This research was funded by FONDECYT initiation 11150624 and FONDECYT Regular 1190928 to MV-G and the APC was funded by FONDECYT Regular 1190928 to MV-G.

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Bone marrow mesenchymal stem cells
  • Cancer stem cells
  • Cisplatin
  • Small extracellular vesicles
  • Spheroids
  • Tumor microenvironment

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