PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation.
Adult
Aged
Aged, 80 and over
Brain Neoplasms
/ genetics
Cells, Cultured
Cohort Studies
Disease Progression
Female
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Glioblastoma
/ genetics
Humans
Macrophage Activation
/ genetics
Macrophages
/ metabolism
Male
Microglia
/ metabolism
Middle Aged
Protein Disulfide-Isomerases
/ genetics
Tumor Microenvironment
/ genetics
IL6
PDIA3
STAT3
glioma
microglia
punicalagin
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
03 Nov 2020
03 Nov 2020
Historique:
received:
29
09
2020
revised:
29
10
2020
accepted:
31
10
2020
entrez:
6
11
2020
pubmed:
7
11
2020
medline:
12
3
2021
Statut:
epublish
Résumé
The glioblastoma (GB) microenvironment includes cells of the innate immune system identified as glioma-associated microglia/macrophages (GAMs) that are still poorly characterized. A potential role on the mechanisms regulating GAM activity might be played by the endoplasmic reticulum protein ERp57/PDIA3 (protein disulfide-isomerase A3), the modulation of which has been reported in a variety of cancers. Moreover, by using The Cancer Genome Atlas database, we found that overexpression of PDIA3 correlated with about 55% reduction of overall survival of glioma patients. Therefore, we analyzed the expression of ERp57/PDIA3 using specimens obtained after surgery from 18 GB patients. Immunohistochemical analysis of tumor samples revealed ERp57/PDIA3 expression in GB cells as well as in GAMs. The ERp57/PDIA3 levels were higher in GAMs than in the microglia present in the surrounding parenchyma. Therefore, we studied the role of PDIA3 modulation in microglia-glioma interaction, based on the ability of conditioned media collected from human GB cells to induce the activation of microglial cells. The results indicated that reduced PDIA3 expression/activity in GB cells significantly limited the microglia pro-tumor polarization towards the M2 phenotype and the production of pro-inflammatory factors. Our data support a role of PDIA3 expression in GB-mediated protumor activation of microglia.
Identifiants
pubmed: 33153019
pii: ijms21218214
doi: 10.3390/ijms21218214
pmc: PMC7662700
pii:
doi:
Substances chimiques
Protein Disulfide-Isomerases
EC 5.3.4.1
PDIA3 protein, human
EC 5.3.4.1.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Università Cattolica Del Sacro Cuore
ID : Fondi Ateneo 2018
Organisme : Università Cattolica Del Sacro Cuore
ID : Fondi Ateneo 2019
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