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

Int J Mol Sci

Cancer Signaling Unit, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), 31008 Pamplona, Spain.

Published: October 2021

AI Article Synopsis

  • * Researchers found that MR activation can inhibit the growth of GBM cells and self-renewal of glioma stem cells (GSCs), with low MR expression correlating to poorer survival rates in certain glioma subtypes.
  • * The MR antagonist spironolactone (SPI) paradoxically promotes GBM cell proliferation and radioprotection, suggesting that while MR signaling is generally anti-proliferative in GBM, SPI might not be effective as a cancer treatment

Article Abstract

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, expression inversely correlates with tumor grade. Furthermore, low 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584062PMC
http://dx.doi.org/10.3390/ijms222111656DOI Listing

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