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

被引:6
作者
Aldaz, Paula [1 ,2 ]
Fernandez-Celis, Amaya [2 ,3 ]
Lopez-Andres, Natalia [2 ,3 ]
Arozarena, Imanol [1 ,2 ]
机构
[1] Univ Publ Navarra UPNA, Hosp Univ Navarra HUN, Canc Signaling Unit, Navarrabiomed, Pamplona 31008, Spain
[2] Hlth Res Inst Navarre IdiSNA, Pamplona 31008, Spain
[3] Univ Publ Navarra UPNA, Hosp Univ Navarra HUN, Cardiovasc Translat Res Unit, Navarrabiomed, Pamplona 31008, Spain
关键词
glioma; mineralocorticoid receptor; spironolactone; glucocorticoid receptor; dexamethasone; SURVIVAL; RESISTANCE;
D O I
10.3390/ijms222111656
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:14
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