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Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma

The majority of glioblastoma (GBM) patients require the administration of dexamethasone (DEXA) to reduce brain inflammation. DEXA activates the glucocorticoid receptor (GR), which can consequently crosstalk with the mineralocorticoid receptor (MR). However, while GR signaling is well studied in GBM,...

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Autores principales: Aldaz, Paula, Fernández-Celis, Amaya, López-Andrés, Natalia, Arozarena, Imanol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584062/
https://www.ncbi.nlm.nih.gov/pubmed/34769089
http://dx.doi.org/10.3390/ijms222111656
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author Aldaz, Paula
Fernández-Celis, Amaya
López-Andrés, Natalia
Arozarena, Imanol
author_facet Aldaz, Paula
Fernández-Celis, Amaya
López-Andrés, Natalia
Arozarena, Imanol
author_sort Aldaz, Paula
collection PubMed
description The majority of glioblastoma (GBM) patients require the administration of dexamethasone (DEXA) to reduce brain inflammation. DEXA activates the glucocorticoid receptor (GR), which can consequently crosstalk with the mineralocorticoid receptor (MR). However, while GR signaling is well studied in GBM, little is known about the MR in brain tumors. We examined the implication of the MR in GBM considering its interplay with DEXA. Together with gene expression studies in patient cohorts, we used human GBM cell lines and patient-derived glioma stem cells (GSCs) to assess the impact of MR activation and inhibition on cell proliferation, response to radiotherapy, and self-renewal capacity. We show that in glioma patients, MR expression inversely correlates with tumor grade. Furthermore, low MR expression correlates with poorer survival in low grade glioma while in GBM the same applies to classical and mesenchymal subtypes, but not proneural tumors. MR activation by aldosterone suppresses the growth of some GBM cell lines and GSC self-renewal. In GBM cells, the MR antagonist spironolactone (SPI) can promote proliferation, radioprotection and cooperate with DEXA. In summary, we propose that MR signaling is anti-proliferative in GBM cells and blocks the self-renewal of GSCs. Contrary to previous evidence obtained in other cancer types, our results suggest that SPI has no compelling anti-neoplastic potential in GBM.
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spelling pubmed-85840622021-11-12 Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma Aldaz, Paula Fernández-Celis, Amaya López-Andrés, Natalia Arozarena, Imanol Int J Mol Sci Article The majority of glioblastoma (GBM) patients require the administration of dexamethasone (DEXA) to reduce brain inflammation. DEXA activates the glucocorticoid receptor (GR), which can consequently crosstalk with the mineralocorticoid receptor (MR). However, while GR signaling is well studied in GBM, little is known about the MR in brain tumors. We examined the implication of the MR in GBM considering its interplay with DEXA. Together with gene expression studies in patient cohorts, we used human GBM cell lines and patient-derived glioma stem cells (GSCs) to assess the impact of MR activation and inhibition on cell proliferation, response to radiotherapy, and self-renewal capacity. We show that in glioma patients, MR expression inversely correlates with tumor grade. Furthermore, low MR expression correlates with poorer survival in low grade glioma while in GBM the same applies to classical and mesenchymal subtypes, but not proneural tumors. MR activation by aldosterone suppresses the growth of some GBM cell lines and GSC self-renewal. In GBM cells, the MR antagonist spironolactone (SPI) can promote proliferation, radioprotection and cooperate with DEXA. In summary, we propose that MR signaling is anti-proliferative in GBM cells and blocks the self-renewal of GSCs. Contrary to previous evidence obtained in other cancer types, our results suggest that SPI has no compelling anti-neoplastic potential in GBM. MDPI 2021-10-28 /pmc/articles/PMC8584062/ /pubmed/34769089 http://dx.doi.org/10.3390/ijms222111656 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aldaz, Paula
Fernández-Celis, Amaya
López-Andrés, Natalia
Arozarena, Imanol
Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma
title Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma
title_full Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma
title_fullStr Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma
title_full_unstemmed Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma
title_short Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma
title_sort novel insights into the role of the mineralocorticoid receptor in human glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584062/
https://www.ncbi.nlm.nih.gov/pubmed/34769089
http://dx.doi.org/10.3390/ijms222111656
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