P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression.
Animals
Antineoplastic Agents
/ pharmacology
Brain Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cells, Cultured
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
/ drug effects
Glioblastoma
/ drug therapy
HEK293 Cells
Humans
Macrophages
/ metabolism
Male
Mice, Inbred C57BL
Mice, SCID
Microglia
/ metabolism
Neoplasms, Experimental
/ drug therapy
P-Selectin
/ antagonists & inhibitors
Tumor Microenvironment
/ drug effects
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 03 2021
26 03 2021
Historique:
received:
11
08
2020
accepted:
01
03
2021
entrez:
27
3
2021
pubmed:
28
3
2021
medline:
13
4
2021
Statut:
epublish
Résumé
Glioblastoma (GB) is a highly invasive type of brain cancer exhibiting poor prognosis. As such, its microenvironment plays a crucial role in its progression. Among the brain stromal cells, the microglia were shown to facilitate GB invasion and immunosuppression. However, the reciprocal mechanisms by which GB cells alter microglia/macrophages behavior are not fully understood. We propose that these mechanisms involve adhesion molecules such as the Selectins family. These proteins are involved in immune modulation and cancer immunity. We show that P-selectin mediates microglia-enhanced GB proliferation and invasion by altering microglia/macrophages activation state. We demonstrate these findings by pharmacological and molecular inhibition of P-selectin which leads to reduced tumor growth and increased survival in GB mouse models. Our work sheds light on tumor-associated microglia/macrophage function and the mechanisms by which GB cells suppress the immune system and invade the brain, paving the way to exploit P-selectin as a target for GB therapy.
Identifiants
pubmed: 33771989
doi: 10.1038/s41467-021-22186-0
pii: 10.1038/s41467-021-22186-0
pmc: PMC7997963
doi:
Substances chimiques
Antineoplastic Agents
0
P-Selectin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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