Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells
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 wi...
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doaj-de702f85209e4659a9e83390725d75252020-11-25T01:50:57ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-10-012020497210.3390/ijms20204972ijms20204972Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem CellsNelly Vera0Stephanie Acuña-Gallardo1Felipe Grünenwald2Albano Caceres-Verschae3Ornella Realini4Rodrigo Acuña5Alvaro Lladser6Sebastián E. Illanes7Manuel Varas-Godoy8Laboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, ChileLaboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, ChileLaboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, ChileLaboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, ChileLaboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, ChileCentro de Fisiología Celular e Integrativa, Facultad de Medicina, Universidad del Desarrollo, Santiago 7610658, ChileLaboratory of Immunoncology, Fundación Ciencia & Vida, Santiago 7780272, ChileLaboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, ChileLaboratory of Reproductive Biology, Center for Biomedical Research, Faculty of Medicine, Universidad de Los Andes, Santiago 7620001, ChileDespite 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.https://www.mdpi.com/1422-0067/20/20/4972small extracellular vesiclescancer stem cellsspheroidscisplatintumor microenvironmentbone marrow mesenchymal stem cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nelly Vera Stephanie Acuña-Gallardo Felipe Grünenwald Albano Caceres-Verschae Ornella Realini Rodrigo Acuña Alvaro Lladser Sebastián E. Illanes Manuel Varas-Godoy |
spellingShingle |
Nelly Vera Stephanie Acuña-Gallardo Felipe Grünenwald Albano Caceres-Verschae Ornella Realini Rodrigo Acuña Alvaro Lladser Sebastián E. Illanes Manuel Varas-Godoy 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 small extracellular vesicles cancer stem cells spheroids cisplatin tumor microenvironment bone marrow mesenchymal stem cells |
author_facet |
Nelly Vera Stephanie Acuña-Gallardo Felipe Grünenwald Albano Caceres-Verschae Ornella Realini Rodrigo Acuña Alvaro Lladser Sebastián E. Illanes Manuel Varas-Godoy |
author_sort |
Nelly Vera |
title |
Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells |
title_short |
Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells |
title_full |
Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells |
title_fullStr |
Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells |
title_full_unstemmed |
Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells |
title_sort |
small extracellular vesicles released from ovarian cancer spheroids in response to cisplatin promote the pro-tumorigenic activity of mesenchymal stem cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2019-10-01 |
description |
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. |
topic |
small extracellular vesicles cancer stem cells spheroids cisplatin tumor microenvironment bone marrow mesenchymal stem cells |
url |
https://www.mdpi.com/1422-0067/20/20/4972 |
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