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Glioblastoma-Associated Microglia Reprogramming Is Mediated by Functional Transfer of Extracellular miR-21.
Abels, Erik R; Maas, Sybren L N; Nieland, Lisa; Wei, Zhiyun; Cheah, Pike See; Tai, Eric; Kolsteeg, Christy-Joy; Dusoswa, Sophie A; Ting, David T; Hickman, Suzanne; El Khoury, Joseph; Krichevsky, Anna M; Broekman, Marike L D; Breakefield, Xandra O.
Afiliação
  • Abels ER; Departments of Neurology and Radiology, Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA. Electronic address: eabels@mgh.harvard.edu.
  • Maas SLN; Department of Neurosurgery, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 CX Utrecht, the Netherlands.
  • Nieland L; Departments of Neurology and Radiology, Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA.
  • Wei Z; Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Cheah PS; Departments of Neurology and Radiology, Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA; Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia.
  • Tai E; Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Kolsteeg CJ; Departments of Neurology and Radiology, Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA.
  • Dusoswa SA; Department of Molecular Cell Biology and Immunology, Amsterdam Infection & Immunology Institute and Cancer Center Amsterdam, Amsterdam UMC, 1081 HZ Amsterdam, the Netherlands.
  • Ting DT; Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Hickman S; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • El Khoury J; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
  • Krichevsky AM; Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Broekman MLD; Department of Neurosurgery, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; Department of Neurosurgery, Haaglanden Medical Center, 2512 VA The Hague, the Netherlands.
  • Breakefield XO; Departments of Neurology and Radiology, Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA 02129, USA. Electronic address: breakefield@hms.harvard.edu.
Cell Rep ; 28(12): 3105-3119.e7, 2019 09 17.
Article em En | MEDLINE | ID: mdl-31533034
ABSTRACT
Gliomas are primary, diffusely infiltrating brain tumors. Microglia are innate immune cells in the CNS and make up a substantial portion of the tumor mass. Glioma cells shape their microenvironment, communicating with and reprogramming surrounding cells, resulting in enhanced angiogenesis, immune suppression, and remodeling of the extracellular matrix. Glioma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Mouse glioma cells stably expressing a palmitoylated GFP to label EVs were implanted intracranially into syngeneic miR-21-null mice. Here, we demonstrate functional delivery of miR-21, regulating specific downstream mRNA targets in microglia after uptake of tumor-derived EVs. These findings attest to EV-dependent microRNA delivery as studied in an in vivo-based model and provide insight into the reprograming of microglial cells by tumor cells to create a favorable microenvironment for cancer progression.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: RNA Neoplásico / Comunicação Celular / Microglia / Glioblastoma / MicroRNAs / Reprogramação Celular / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: RNA Neoplásico / Comunicação Celular / Microglia / Glioblastoma / MicroRNAs / Reprogramação Celular / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article