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PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation
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/PD...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662700/ https://www.ncbi.nlm.nih.gov/pubmed/33153019 http://dx.doi.org/10.3390/ijms21218214 |
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author | Chiavari, Marta Ciotti, Gabriella Maria Pia Canonico, Francesco Altieri, Fabio Lacal, Pedro Miguel Graziani, Grazia Navarra, Pierluigi Lisi, Lucia |
author_facet | Chiavari, Marta Ciotti, Gabriella Maria Pia Canonico, Francesco Altieri, Fabio Lacal, Pedro Miguel Graziani, Grazia Navarra, Pierluigi Lisi, Lucia |
author_sort | Chiavari, Marta |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7662700 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76627002020-11-14 PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation Chiavari, Marta Ciotti, Gabriella Maria Pia Canonico, Francesco Altieri, Fabio Lacal, Pedro Miguel Graziani, Grazia Navarra, Pierluigi Lisi, Lucia Int J Mol Sci Article 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. MDPI 2020-11-03 /pmc/articles/PMC7662700/ /pubmed/33153019 http://dx.doi.org/10.3390/ijms21218214 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chiavari, Marta Ciotti, Gabriella Maria Pia Canonico, Francesco Altieri, Fabio Lacal, Pedro Miguel Graziani, Grazia Navarra, Pierluigi Lisi, Lucia PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation |
title | PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation |
title_full | PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation |
title_fullStr | PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation |
title_full_unstemmed | PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation |
title_short | PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation |
title_sort | pdia3 expression in glioblastoma modulates macrophage/microglia pro-tumor activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662700/ https://www.ncbi.nlm.nih.gov/pubmed/33153019 http://dx.doi.org/10.3390/ijms21218214 |
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