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TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients

The survival of patients with glioblastoma (GBM) is poor. The main cause is the presence of glioma stem cells (GSCs), exceptionally resistant to temozolomide (TMZ) treatment. This last may be related to the heterogeneous expression of ion channels, among them TRPML2. Its mRNA expression was evaluate...

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Autores principales: Morelli, Maria Beatrice, Nabissi, Massimo, Amantini, Consuelo, Maggi, Federica, Ricci-Vitiani, Lucia, Pallini, Roberto, Santoni, Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738251/
https://www.ncbi.nlm.nih.gov/pubmed/36499683
http://dx.doi.org/10.3390/ijms232315356
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author Morelli, Maria Beatrice
Nabissi, Massimo
Amantini, Consuelo
Maggi, Federica
Ricci-Vitiani, Lucia
Pallini, Roberto
Santoni, Giorgio
author_facet Morelli, Maria Beatrice
Nabissi, Massimo
Amantini, Consuelo
Maggi, Federica
Ricci-Vitiani, Lucia
Pallini, Roberto
Santoni, Giorgio
author_sort Morelli, Maria Beatrice
collection PubMed
description The survival of patients with glioblastoma (GBM) is poor. The main cause is the presence of glioma stem cells (GSCs), exceptionally resistant to temozolomide (TMZ) treatment. This last may be related to the heterogeneous expression of ion channels, among them TRPML2. Its mRNA expression was evaluated in two different neural stem cell (NS/PC) lines and sixteen GBM stem-like cells by qRT-PCR. The response to TMZ was evaluated in undifferentiated or differentiated GSCs, and in TRPML2-induced or silenced GSCs. The relationship between TRPML2 expression and responsiveness to TMZ treatment was evaluated by MTT assay showing that increased TRPML2 mRNA levels are associated with resistance to TMZ. This research was deepened by qRT-PCR and western blot analysis. PI3K/AKT and JAK/STAT pathways as well as ABC and SLC drug transporters were involved. Finally, the relationship between TRPML2 expression and overall survival (OS) and progression-free survival (PFS) in patient-derived GSCs was evaluated by Kaplan–Meier analysis. The expression of TRPML2 mRNA correlates with worse OS and PFS in GBM patients. Thus, the expression of TRPML2 in GSCs influences the responsiveness to TMZ in vitro and affects OS and PFS in GBM patients.
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spelling pubmed-97382512022-12-11 TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients Morelli, Maria Beatrice Nabissi, Massimo Amantini, Consuelo Maggi, Federica Ricci-Vitiani, Lucia Pallini, Roberto Santoni, Giorgio Int J Mol Sci Article The survival of patients with glioblastoma (GBM) is poor. The main cause is the presence of glioma stem cells (GSCs), exceptionally resistant to temozolomide (TMZ) treatment. This last may be related to the heterogeneous expression of ion channels, among them TRPML2. Its mRNA expression was evaluated in two different neural stem cell (NS/PC) lines and sixteen GBM stem-like cells by qRT-PCR. The response to TMZ was evaluated in undifferentiated or differentiated GSCs, and in TRPML2-induced or silenced GSCs. The relationship between TRPML2 expression and responsiveness to TMZ treatment was evaluated by MTT assay showing that increased TRPML2 mRNA levels are associated with resistance to TMZ. This research was deepened by qRT-PCR and western blot analysis. PI3K/AKT and JAK/STAT pathways as well as ABC and SLC drug transporters were involved. Finally, the relationship between TRPML2 expression and overall survival (OS) and progression-free survival (PFS) in patient-derived GSCs was evaluated by Kaplan–Meier analysis. The expression of TRPML2 mRNA correlates with worse OS and PFS in GBM patients. Thus, the expression of TRPML2 in GSCs influences the responsiveness to TMZ in vitro and affects OS and PFS in GBM patients. MDPI 2022-12-05 /pmc/articles/PMC9738251/ /pubmed/36499683 http://dx.doi.org/10.3390/ijms232315356 Text en © 2022 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
Morelli, Maria Beatrice
Nabissi, Massimo
Amantini, Consuelo
Maggi, Federica
Ricci-Vitiani, Lucia
Pallini, Roberto
Santoni, Giorgio
TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients
title TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients
title_full TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients
title_fullStr TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients
title_full_unstemmed TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients
title_short TRPML2 Mucolipin Channels Drive the Response of Glioma Stem Cells to Temozolomide and Affect the Overall Survival in Glioblastoma Patients
title_sort trpml2 mucolipin channels drive the response of glioma stem cells to temozolomide and affect the overall survival in glioblastoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738251/
https://www.ncbi.nlm.nih.gov/pubmed/36499683
http://dx.doi.org/10.3390/ijms232315356
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