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:	Paula Aldaz, Amaya Fernández-Celis, Natalia López-Andrés, Imanol Arozarena
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	glioma mineralocorticoid receptor spironolactone glucocorticoid receptor dexamethasone Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/4d922a28b7db4094b223a72a8e40437a
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spelling	oai:doaj.org-article:4d922a28b7db4094b223a72a8e40437a2021-11-11T17:07:42ZNovel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma10.3390/ijms2221116561422-00671661-6596https://doaj.org/article/4d922a28b7db4094b223a72a8e40437a2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11656https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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, <i>MR</i> expression inversely correlates with tumor grade. Furthermore, low <i>MR</i> 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.Paula AldazAmaya Fernández-CelisNatalia López-AndrésImanol ArozarenaMDPI AGarticlegliomamineralocorticoid receptorspironolactoneglucocorticoid receptordexamethasoneBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11656, p 11656 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	glioma mineralocorticoid receptor spironolactone glucocorticoid receptor dexamethasone Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	glioma mineralocorticoid receptor spironolactone glucocorticoid receptor dexamethasone Biology (General) QH301-705.5 Chemistry QD1-999 Paula Aldaz Amaya Fernández-Celis Natalia López-Andrés Imanol Arozarena Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma
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, <i>MR</i> expression inversely correlates with tumor grade. Furthermore, low <i>MR</i> 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.
format	article
author	Paula Aldaz Amaya Fernández-Celis Natalia López-Andrés Imanol Arozarena
author_facet	Paula Aldaz Amaya Fernández-Celis Natalia López-Andrés Imanol Arozarena
author_sort	Paula Aldaz
title	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_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_sort	novel insights into the role of the mineralocorticoid receptor in human glioblastoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4d922a28b7db4094b223a72a8e40437a
work_keys_str_mv	AT paulaaldaz novelinsightsintotheroleofthemineralocorticoidreceptorinhumanglioblastoma AT amayafernandezcelis novelinsightsintotheroleofthemineralocorticoidreceptorinhumanglioblastoma AT natalialopezandres novelinsightsintotheroleofthemineralocorticoidreceptorinhumanglioblastoma AT imanolarozarena novelinsightsintotheroleofthemineralocorticoidreceptorinhumanglioblastoma
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Novel Insights into the Role of the Mineralocorticoid Receptor in Human Glioblastoma

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