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Glioblastoma hijacks microglial gene expression to support tumor growth.
Maas, Sybren L N; Abels, Erik R; Van De Haar, Lieke L; Zhang, Xuan; Morsett, Liza; Sil, Srinjoy; Guedes, Joana; Sen, Pritha; Prabhakar, Shilpa; Hickman, Suzanne E; Lai, Charles P; Ting, David T; Breakefield, Xandra O; Broekman, Marike L D; El Khoury, Joseph.
Afiliación
  • Maas SLN; Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Abels ER; Department of Neurosurgery, UMC Utrecht Brain Center, University Medical Center, Utrecht University, 3584 CX, Utrecht, The Netherlands.
  • Van De Haar LL; Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Zhang X; Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Morsett L; Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Sil S; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Guedes J; Cancer Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Sen P; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Prabhakar S; Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
  • Hickman SE; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Lai CP; Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Ting DT; Center for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Breakefield XO; Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • Broekman MLD; Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.
  • El Khoury J; Institute of Atomic and Molecular Sciences/Academia Sinica, 10617, Taipei, Taiwan.
J Neuroinflammation ; 17(1): 120, 2020 Apr 16.
Article en En | MEDLINE | ID: mdl-32299465
ABSTRACT

BACKGROUND:

Glioblastomas are the most common and lethal primary brain tumors. Microglia, the resident immune cells of the brain, survey their environment and respond to pathogens, toxins, and tumors. Glioblastoma cells communicate with microglia, in part by releasing extracellular vesicles (EVs). Despite the presence of large numbers of microglia in glioblastoma, the tumors continue to grow, and these neuroimmune cells appear incapable of keeping the tumor in check. To understand this process, we analyzed gene expression in microglia interacting with glioblastoma cells.

METHODS:

We used RNASeq of isolated microglia to analyze the expression patterns of genes involved in key microglial functions in mice with glioblastoma. We focused on microglia that had taken up tumor-derived EVs and therefore were within and immediately adjacent to the tumor.

RESULTS:

We show that these microglia have downregulated expression of genes involved in sensing tumor cells and tumor-derived danger signals, as well as genes used for tumor killing. In contrast, expression of genes involved in facilitating tumor spread was upregulated. These changes appear to be in part EV-mediated, since intracranial injection of EVs in normal mice led to similar transcriptional changes in microglia. We observed a similar microglial transcriptomic signature when we analyzed datasets from human patients with glioblastoma.

CONCLUSION:

Our data define a microgliaGlioblastoma specific phenotype, whereby glioblastomas have hijacked gene expression in the neuroimmune system to favor avoiding tumor sensing, suppressing the immune response, clearing a path for invasion, and enhancing tumor propagation. For further exploration, we developed an interactive online tool at http//www.glioma-microglia.com with all expression data and additional functional and pathway information for each gene.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Regulación Neoplásica de la Expresión Génica / Microglía / Glioblastoma Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Regulación Neoplásica de la Expresión Génica / Microglía / Glioblastoma Idioma: En Revista: J Neuroinflammation Asunto de la revista: NEUROLOGIA Año: 2020 Tipo del documento: Article