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Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain.
van der Vos, Kristan E; Abels, Erik R; Zhang, Xuan; Lai, Charles; Carrizosa, Esteban; Oakley, Derek; Prabhakar, Shilpa; Mardini, Osama; Crommentuijn, Matheus H W; Skog, Johan; Krichevsky, Anna M; Stemmer-Rachamimov, Anat; Mempel, Thorsten R; El Khoury, Joseph; Hickman, Suzanne E; Breakefield, Xandra O.
Afiliación
  • van der Vos KE; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Abels ER; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Zhang X; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Lai C; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Carrizosa E; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Oakley D; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Prabhakar S; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Mardini O; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Crommentuijn MH; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Skog J; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Krichevsky AM; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Stemmer-Rachamimov A; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Mempel TR; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • El Khoury J; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Hickman SE; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
  • Breakefield XO; Departments of Neurology and Radiology, Massachusetts General Hospital and NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts (K.E.v.d.V., E.R.A., X.Z., C.L., S.P., O.M., M.H.W.C., J.S., X.O.B.); Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Bosto
Neuro Oncol ; 18(1): 58-69, 2016 Jan.
Article en En | MEDLINE | ID: mdl-26433199
ABSTRACT

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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Microglía / Glioblastoma / MicroARNs / Vesículas Extracelulares / Macrófagos Límite: Animals / Humans Idioma: En Revista: Neuro Oncol Asunto de la revista: NEOPLASIAS / NEUROLOGIA Año: 2016 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Microglía / Glioblastoma / MicroARNs / Vesículas Extracelulares / Macrófagos Límite: Animals / Humans Idioma: En Revista: Neuro Oncol Asunto de la revista: NEOPLASIAS / NEUROLOGIA Año: 2016 Tipo del documento: Article