Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain
| العنوان: | Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain |
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| المؤلفون: | Matheus H.W. Crommentuijn, Anat Stemmer-Rachamimov, Kristan E. van der Vos, Erik R. Abels, Xuan Zhang, Derek H. Oakley, Johan Skog, Osama Mardini, Xandra O. Breakefield, Charles P. Lai, Anna M. Krichevsky, Suzanne E. Hickman, Thorsten R. Mempel, Joseph El Khoury, Esteban Carrizosa, Shilpa Prabhakar |
| المساهمون: | CCA - Cancer biology |
| المصدر: | Neuro-Oncology, 18(1), 58-69. Oxford University Press van der Vos, K E, Abels, E R, Zhang, X, Lai, C, Carrizosa, E, Oakley, D, Prabhakar, S, Mardini, O, Crommentuijn, M H W, Skog, J, Krichevsky, A M, Stemmer-Rachamimov, A, Mempel, T R, El Khoury, J, Hickman, S E & Breakefield, X O 2016, ' Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain ', Neuro-Oncology, vol. 18, no. 1, pp. 58-69 . https://doi.org/10.1093/neuonc/nov244 |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Biology, Proto-Oncogene Proteins c-myc, Extracellular Vesicles, Mice, 03 medical and health sciences, Cell Line, Tumor, Glioma, microRNA, Tumor Cells, Cultured, medicine, Animals, Humans, Macrophage, RNA, Messenger, Messenger RNA, Microglia, Brain Neoplasms, Macrophages, Brain, medicine.disease, Molecular biology, Microvesicles, Cell biology, Mice, Inbred C57BL, MicroRNAs, Microscopy, Fluorescence, Multiphoton, 030104 developmental biology, medicine.anatomical_structure, Oncology, Basic and Translational Investigations, Neurology (clinical), Glioblastoma, Intravital microscopy, Extracellular RNA |
| الوصف: | Background To understand the ability of gliomas to manipulate their microenvironment, we visualized the transfer of vesicles and the effects of tumor-released extracellular RNA on the phenotype of microglia in culture and in vivo. Methods Extracellular vesicles (EVs) released from primary human glioblastoma (GBM) cells were isolated and microRNAs (miRNAs) were analyzed. Primary mouse microglia were exposed to GBM-EVs, and their uptake and effect on proliferation and levels of specific miRNAs, mRNAs, and proteins were analyzed. For in vivo analysis, mouse glioma cells were implanted in the brains of mice, and EV release and uptake by microglia and monocytes/macrophages were monitored by intravital 2-photon microscopy, immunohistochemistry, and fluorescence activated cell sorting analysis, as well as RNA and protein levels. Results Microglia avidly took up GBM-EVs, leading to increased proliferation and shifting of their cytokine profile toward immune suppression. High levels of miR-451/miR-21 in GBM-EVs were transferred to microglia with a decrease in the miR-451/miR-21 target c-Myc mRNA. In in vivo analysis, we directly visualized release of EVs from glioma cells and their uptake by microglia and monocytes/macrophages in brain. Dissociated microglia and monocytes/macrophages from tumor-bearing brains revealed increased levels of miR-21 and reduced levels of c-Myc mRNA. Conclusions Intravital microscopy confirms the release of EVs from gliomas and their uptake into microglia and monocytes/macrophages within the brain. Our studies also support functional effects of GBM-released EVs following uptake into microglia, associated in part with increased miRNA levels, decreased target mRNAs, and encoded proteins, presumably as a means for the tumor to manipulate its environs. |
| اللغة: | English |
| تدمد: | 1522-8517 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::521953dbe90ee3238fc8cbafbdc5a322 https://doi.org/10.1093/neuonc/nov244 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....521953dbe90ee3238fc8cbafbdc5a322 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15228517 |
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