Journal
NANOMEDICINE
Volume 15, Issue 10, Pages 1001-1018Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2019-0431
Keywords
cancer; extracellular vesicles; glioma; regulatory cells; tumor microenvironment
Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [302879/2017-0]
- INCT.MCTI/CNPq/CAPES/FAPERGS [465671/2014-4]
- FAPERGS PQG [17/2551-0000 970-3]
- Natural Sciences and Engineering Research Council of Canada (NSERC) [RGPIN-2016-05867]
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Aim: To characterize a method to isolate glioma-derived extracellular vesicles (GEVs) and understand their role in immune system modulation and glioma progression. Materials & methods: GEVs were isolated by differential centrifugation from C6 cell supernatant and characterized by size and expression of CD9, HSP70, CD39 and CD73. The glioma model was performed by injecting C6 glioma cells into the right striatum of Wistar rats in the following groups: controls (C6 cells alone), coinjection (C6 cells + GEVs) and GEVs by intranasal administration followed by immune cells, tumor size and cells proliferation analyses. Results: GEVs presented uniform size (175 nm), expressed CD9, HSP70, CD39, CD73 and produced adenosine. In vivo, we observed a reduction in tumor size, in cell proliferation (Ki-67) and in a regulatory cell marker (FoxP3). Conclusion: GEVs, administered before or at tumor challenge, have antiproliferative properties and reduce regulatory cells in the glioma microenvironment. Graphical abstract
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