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...
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| Format: | Article |
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8214 |
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| author | Marta Chiavari Gabriella Maria Pia Ciotti Francesco Canonico Fabio Altieri Pedro Miguel Lacal Grazia Graziani Pierluigi Navarra Lucia Lisi |
| author_facet | Marta Chiavari Gabriella Maria Pia Ciotti Francesco Canonico Fabio Altieri Pedro Miguel Lacal Grazia Graziani Pierluigi Navarra Lucia Lisi |
| author_sort | Marta Chiavari |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T15:08:19Z |
| format | Article |
| id | doaj.art-a8cd318a79d2401f8261625b0df174ee |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:08:19Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a8cd318a79d2401f8261625b0df174ee2023-11-20T19:35:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012121821410.3390/ijms21218214PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor ActivationMarta Chiavari0Gabriella Maria Pia Ciotti1Francesco Canonico2Fabio Altieri3Pedro Miguel Lacal4Grazia Graziani5Pierluigi Navarra6Lucia Lisi7Dipartimento di Bioetica e Sicurezza, Sezione di Farmacologia—Catholic University Medical School, 00168 Rome, ItalyDipartimento di Bioetica e Sicurezza, Sezione di Farmacologia—Catholic University Medical School, 00168 Rome, ItalyDipartimento di Scienze Cardiovascolari e Toraciche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University Medical School, 00168 Rome, ItalyDipartimento di Scienze Biochimiche “A. Rossi Fanelli”, Sapienza University, P.le A. Moro 5, 00185 Rome, ItalyIDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, ItalyDepartment of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, ItalyDipartimento di Bioetica e Sicurezza, Sezione di Farmacologia—Catholic University Medical School, 00168 Rome, ItalyDipartimento di Bioetica e Sicurezza, Sezione di Farmacologia—Catholic University Medical School, 00168 Rome, ItalyThe 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.https://www.mdpi.com/1422-0067/21/21/8214PDIA3STAT3IL6microgliagliomapunicalagin |
| spellingShingle | Marta Chiavari Gabriella Maria Pia Ciotti Francesco Canonico Fabio Altieri Pedro Miguel Lacal Grazia Graziani Pierluigi Navarra Lucia Lisi PDIA3 Expression in Glioblastoma Modulates Macrophage/Microglia Pro-Tumor Activation International Journal of Molecular Sciences PDIA3 STAT3 IL6 microglia glioma punicalagin |
| 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 | PDIA3 STAT3 IL6 microglia glioma punicalagin |
| url | https://www.mdpi.com/1422-0067/21/21/8214 |
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