Small Extracellular Vesicles Released from Ovarian Cancer Spheroids in Response to Cisplatin Promote the Pro-Tumorigenic Activity of Mesenchymal Stem Cells
Journal
International Journal of Molecular Sciences
ISSN
1422-0067
Date Issued
2019
Author(s)
Nelly Vera
Stephanie Acuña-Gallardo
Felipe Grünenwald
Albano Caceres-Verschae
Ornella Realini
Alvaro Lladser
Sebastián E. Illanes
Manuel Varas-Godoy
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Cite this document
Vera, N., Acuña-Gallardo, S., Grünenwald, F., Caceres-Verschae, A., Realini, O., Acuña, R., Lladser, A., Illanes, S. E., & Varas-Godoy, M. (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(20), 4972. https://doi.org/10.3390/ijms20204972
Subjects
small extracellular vesicles
;
cancer stemcells
;
spheroids
;
cisplatin
;
tumormicroenvironment
;
bone marrow mesenchymal stem cells
;
cell line, tumor
;
cell transformation, neoplastic
;
cisplatin
;
cytokines
;
exosomes
;
extracellular vesicles
;
female
;
gene expression
;
humans
;
mesenchymal stem cells
;
metalloproteases
;
neovascularization, pathologic
;
ovarian neoplasms
;
spheroids, cellular
;
tumor microenvironment
;
cisplatin
;
gelatinase a
;
interleukin 6
;
interleukin 8
;
interstitial collagenase
;
monocyte chemotactic protein 1
;
vasculotropin
;
vasculotropin a
;
cisplatin
;
cytokine
;
metalloproteinase
;
article
;
bioassay
;
bone marrow derived mesenchymal stem cell
;
cancer cell culture
;
carcinogenic activity
;
cell isolation
;
cell migration
;
cell migration assay
;
cell size
;
cell tracking
;
colony formation
;
controlled study
;
down regulation
;
exosome
;
female
;
human
;
human cell
;
luminex assay
;
mesenchymal stem cell
;
microscopy
;
ovary cancer
;
oxidative phosphorylation
;
protein expression
;
real time reverse transcription polymerase chain reaction
;
rna isolation
;
transmission electron microscopy
;
tube formation assay
;
tumor growth
;
tumor microenvironment
;
tumor spheroid
;
western blotting
;
cell transformation
;
drug effect
;
exosome
;
gene expression
;
genetics
;
mesenchymal stem cell
;
metabolism
;
multicellular spheroid
;
neovascularization (pathology)
;
ovary tumor
;
pathology
;
tumor cell line
;
ultrastructure