Glioblastoma hijacks microglial gene expression to support tumor growth.
Exosomes
Extracellular vesicles
Glioblastoma
Glioma
Macrophages
Microglia
Microvesicles
RNASeq
Sensome
TGF-β
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
16 Apr 2020
16 Apr 2020
Historique:
received:
10
12
2019
accepted:
31
03
2020
entrez:
18
4
2020
pubmed:
18
4
2020
medline:
29
1
2021
Statut:
epublish
Résumé
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. 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. 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. Our data define a microglia
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
Our data define a microglia
Identifiants
pubmed: 32299465
doi: 10.1186/s12974-020-01797-2
pii: 10.1186/s12974-020-01797-2
pmc: PMC7164149
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
120Subventions
Organisme : NIAID NIH HHS
ID : T32 AI007061
Pays : United States
Organisme : NCI NIH HHS
ID : CA069246
Pays : United States
Organisme : NIH Office of the Director
ID : CA179563
Organisme : NIA NIH HHS
ID : RF1 AG051506
Pays : United States
Organisme : NIH HHS
ID : R01 AI119065
Pays : United States
Organisme : NIH HHS
ID : 1RF1 AG051506
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA069246
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA232103
Pays : United States
Organisme : NCI NIH HHS
ID : CA179563
Pays : United States
Organisme : NCI NIH HHS
ID : CA232103
Pays : United States
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