Cargando…
Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR
Glioblastoma multiforme (GBM) is the most frequent and deadly brain tumor. Many sphingolipids are crucial players in the regulation of glioma cell growth as well as in the response to different chemotherapeutic drugs. In particular, ceramide (Cer) is a tumor suppressor lipid, able to induce antiprol...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607229/ https://www.ncbi.nlm.nih.gov/pubmed/37895074 http://dx.doi.org/10.3390/ijms242015394 |
_version_ | 1785127497046687744 |
---|---|
author | Bassi, Rosaria Dei Cas, Michele Tringali, Cristina Compostella, Federica Paroni, Rita Giussani, Paola |
author_facet | Bassi, Rosaria Dei Cas, Michele Tringali, Cristina Compostella, Federica Paroni, Rita Giussani, Paola |
author_sort | Bassi, Rosaria |
collection | PubMed |
description | Glioblastoma multiforme (GBM) is the most frequent and deadly brain tumor. Many sphingolipids are crucial players in the regulation of glioma cell growth as well as in the response to different chemotherapeutic drugs. In particular, ceramide (Cer) is a tumor suppressor lipid, able to induce antiproliferative and apoptotic responses in different types of tumors including GBM, most of which overexpress the epidermal growth factor receptor variant III (EGFRvIII). In this paper, we investigated whether Cer metabolism is altered in the U87MG human glioma cell line overexpressing EGFRvIII (EGFR+ cells) to elucidate their possible interplay in the mechanisms regulating GBM survival properties and the response to the alkylating agent temozolomide (TMZ). Notably, we demonstrated that a low dose of TMZ significantly increases Cer levels in U87MG cells but slightly in EGFR+ cells (sensitive and resistant to TMZ, respectively). Moreover, the inhibition of the synthesis of complex sphingolipids made EGFR+ cells sensitive to TMZ, thus involving Cer accumulation/removal in TMZ resistance of GBM cells. This suggests that the enhanced resistance of EGFR+ cells to TMZ is dependent on Cer metabolism. Altogether, our results indicate that EGFRvIII expression confers a TMZ-resistance phenotype to U87MG glioma cells by counteracting Cer increase. |
format | Online Article Text |
id | pubmed-10607229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106072292023-10-28 Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR Bassi, Rosaria Dei Cas, Michele Tringali, Cristina Compostella, Federica Paroni, Rita Giussani, Paola Int J Mol Sci Article Glioblastoma multiforme (GBM) is the most frequent and deadly brain tumor. Many sphingolipids are crucial players in the regulation of glioma cell growth as well as in the response to different chemotherapeutic drugs. In particular, ceramide (Cer) is a tumor suppressor lipid, able to induce antiproliferative and apoptotic responses in different types of tumors including GBM, most of which overexpress the epidermal growth factor receptor variant III (EGFRvIII). In this paper, we investigated whether Cer metabolism is altered in the U87MG human glioma cell line overexpressing EGFRvIII (EGFR+ cells) to elucidate their possible interplay in the mechanisms regulating GBM survival properties and the response to the alkylating agent temozolomide (TMZ). Notably, we demonstrated that a low dose of TMZ significantly increases Cer levels in U87MG cells but slightly in EGFR+ cells (sensitive and resistant to TMZ, respectively). Moreover, the inhibition of the synthesis of complex sphingolipids made EGFR+ cells sensitive to TMZ, thus involving Cer accumulation/removal in TMZ resistance of GBM cells. This suggests that the enhanced resistance of EGFR+ cells to TMZ is dependent on Cer metabolism. Altogether, our results indicate that EGFRvIII expression confers a TMZ-resistance phenotype to U87MG glioma cells by counteracting Cer increase. MDPI 2023-10-20 /pmc/articles/PMC10607229/ /pubmed/37895074 http://dx.doi.org/10.3390/ijms242015394 Text en © 2023 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 Bassi, Rosaria Dei Cas, Michele Tringali, Cristina Compostella, Federica Paroni, Rita Giussani, Paola Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR |
title | Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR |
title_full | Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR |
title_fullStr | Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR |
title_full_unstemmed | Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR |
title_short | Ceramide Is Involved in Temozolomide Resistance in Human Glioblastoma U87MG Overexpressing EGFR |
title_sort | ceramide is involved in temozolomide resistance in human glioblastoma u87mg overexpressing egfr |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10607229/ https://www.ncbi.nlm.nih.gov/pubmed/37895074 http://dx.doi.org/10.3390/ijms242015394 |
work_keys_str_mv | AT bassirosaria ceramideisinvolvedintemozolomideresistanceinhumanglioblastomau87mgoverexpressingegfr AT deicasmichele ceramideisinvolvedintemozolomideresistanceinhumanglioblastomau87mgoverexpressingegfr AT tringalicristina ceramideisinvolvedintemozolomideresistanceinhumanglioblastomau87mgoverexpressingegfr AT compostellafederica ceramideisinvolvedintemozolomideresistanceinhumanglioblastomau87mgoverexpressingegfr AT paronirita ceramideisinvolvedintemozolomideresistanceinhumanglioblastomau87mgoverexpressingegfr AT giussanipaola ceramideisinvolvedintemozolomideresistanceinhumanglioblastomau87mgoverexpressingegfr |