Downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes contributes to antitumor effects in a mouse model of malignant glioma.
Animals
Antineoplastic Agents
/ pharmacology
Cell Line
Chemokine CCL2
/ genetics
Chemokine CXCL10
/ genetics
Disease Models, Animal
Down-Regulation
/ drug effects
Glioma
/ drug therapy
Humans
Male
Mice
Mice, Inbred C57BL
Microglia
/ drug effects
Receptors, CCR2
/ genetics
Receptors, CXCR3
/ genetics
Stem Cells
/ drug effects
Tumor Microenvironment
/ drug effects
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 09 2020
17 09 2020
Historique:
received:
20
10
2019
accepted:
17
08
2020
entrez:
18
9
2020
pubmed:
19
9
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Glioblastoma multiforme involves glioma stem cells (GSCs) that are resistant to various therapeutic approaches. Here, we studied the importance of paracrine signaling in the glioma microenvironment by focusing on the celecoxib-mediated role of chemokines C-C motif ligand 2 (CCL2), C-X-C ligand 10 (CXCL10), and their receptors, CCR2 and CXCR3, in GSCs and a GSC-bearing malignant glioma model. C57BL/6 mice were injected with orthotopic GSCs intracranially and divided into groups administered either 10 or 30 mg/kg celecoxib, or saline to examine the antitumor effects associated with chemokine expression. In GSCs, we analyzed cell viability and expression of chemokines and their receptors in the presence/absence of celecoxib. In the malignant glioma model, celecoxib exhibited antitumor effects in a dose dependent manner and decreased protein and mRNA levels of Ccl2 and CxcL10 and Cxcr3 but not of Ccr2. CCL2 and CXCL10 co-localized with Nestin
Identifiants
pubmed: 32943658
doi: 10.1038/s41598-020-71857-3
pii: 10.1038/s41598-020-71857-3
pmc: PMC7499211
doi:
Substances chimiques
Antineoplastic Agents
0
CCL2 protein, human
0
CCR2 protein, human
0
CXCL10 protein, human
0
CXCR3 protein, human
0
Chemokine CCL2
0
Chemokine CXCL10
0
Receptors, CCR2
0
Receptors, CXCR3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
15286Références
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