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Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone
Pediatric high-grade gliomas (pHGG) are brain tumors occurring in children and adolescents associated with a dismal prognosis despite existing treatments. Therapeutic failure in both adult and pHGG has been partially imputed to glioma stem cells (GSC), a subset of cancer cells endowed with stem-like...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276389/ https://www.ncbi.nlm.nih.gov/pubmed/37328883 http://dx.doi.org/10.1186/s40478-023-01586-x |
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author | Da-Veiga, Marc-Antoine Coppieters, Natacha Lombard, Arnaud Rogister, Bernard Neirinckx, Virginie Piette, Caroline |
author_facet | Da-Veiga, Marc-Antoine Coppieters, Natacha Lombard, Arnaud Rogister, Bernard Neirinckx, Virginie Piette, Caroline |
author_sort | Da-Veiga, Marc-Antoine |
collection | PubMed |
description | Pediatric high-grade gliomas (pHGG) are brain tumors occurring in children and adolescents associated with a dismal prognosis despite existing treatments. Therapeutic failure in both adult and pHGG has been partially imputed to glioma stem cells (GSC), a subset of cancer cells endowed with stem-like cell potential and malignant, invasive, adaptative, and treatment-resistant capabilities. Whereas GSC have largely been portrayed in adult tumors, less information has been provided in pHGG. The aim of our study was to comprehensively document the stem-like capacities of seven in-use pediatric glioma cell cultures (Res259, UW479, SF188, KNS42, SF8628, HJSD-DIPG-007 and HJSD-DIPG-012) using parallel in vitro assays assessing stem cell-related protein expression, multipotency, self-renewal and proliferation/quiescence, and in vivo investigation of their tumorigenicity and invasiveness. Data obtained from in vitro experiments revealed glioma subtype-dependent expression of stem cell-related markers and varying abilities for differentiation, self-renewal, and proliferation/quiescence. Among tested cultures, DMG H3-K27 altered cultures displayed a particular pattern of stem-like markers expression and a higher fraction of cells with self-renewal potential. Four cultures displaying distinctive stem-like profiles were further tested for their ability to initiate tumors and invade the brain tissue in mouse orthotopic xenografts. The selected cell cultures all showed a great tumor formation capacity, but only DMG H3-K27 altered cells demonstrated a highly infiltrative phenotype. Interestingly, we detected DMG H3-K27 altered cells relocated in the subventricular zone (SVZ), which has been previously described as a neurogenic area, but also a potential niche for brain tumor cells. Finally, we observed an SVZ-induced phenotypic modulation of the glioma cells, as evidenced by their increased proliferation rate. In conclusion, this study recapitulated a systematic stem-like profiling of various pediatric glioma cell cultures and call to a deeper characterization of DMG H3-K27 altered cells nested in the SVZ. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01586-x. |
format | Online Article Text |
id | pubmed-10276389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-102763892023-06-18 Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone Da-Veiga, Marc-Antoine Coppieters, Natacha Lombard, Arnaud Rogister, Bernard Neirinckx, Virginie Piette, Caroline Acta Neuropathol Commun Research Pediatric high-grade gliomas (pHGG) are brain tumors occurring in children and adolescents associated with a dismal prognosis despite existing treatments. Therapeutic failure in both adult and pHGG has been partially imputed to glioma stem cells (GSC), a subset of cancer cells endowed with stem-like cell potential and malignant, invasive, adaptative, and treatment-resistant capabilities. Whereas GSC have largely been portrayed in adult tumors, less information has been provided in pHGG. The aim of our study was to comprehensively document the stem-like capacities of seven in-use pediatric glioma cell cultures (Res259, UW479, SF188, KNS42, SF8628, HJSD-DIPG-007 and HJSD-DIPG-012) using parallel in vitro assays assessing stem cell-related protein expression, multipotency, self-renewal and proliferation/quiescence, and in vivo investigation of their tumorigenicity and invasiveness. Data obtained from in vitro experiments revealed glioma subtype-dependent expression of stem cell-related markers and varying abilities for differentiation, self-renewal, and proliferation/quiescence. Among tested cultures, DMG H3-K27 altered cultures displayed a particular pattern of stem-like markers expression and a higher fraction of cells with self-renewal potential. Four cultures displaying distinctive stem-like profiles were further tested for their ability to initiate tumors and invade the brain tissue in mouse orthotopic xenografts. The selected cell cultures all showed a great tumor formation capacity, but only DMG H3-K27 altered cells demonstrated a highly infiltrative phenotype. Interestingly, we detected DMG H3-K27 altered cells relocated in the subventricular zone (SVZ), which has been previously described as a neurogenic area, but also a potential niche for brain tumor cells. Finally, we observed an SVZ-induced phenotypic modulation of the glioma cells, as evidenced by their increased proliferation rate. In conclusion, this study recapitulated a systematic stem-like profiling of various pediatric glioma cell cultures and call to a deeper characterization of DMG H3-K27 altered cells nested in the SVZ. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-023-01586-x. BioMed Central 2023-06-16 /pmc/articles/PMC10276389/ /pubmed/37328883 http://dx.doi.org/10.1186/s40478-023-01586-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Da-Veiga, Marc-Antoine Coppieters, Natacha Lombard, Arnaud Rogister, Bernard Neirinckx, Virginie Piette, Caroline Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone |
title | Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone |
title_full | Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone |
title_fullStr | Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone |
title_full_unstemmed | Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone |
title_short | Comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone |
title_sort | comprehensive profiling of stem-like features in pediatric glioma cell cultures and their relation to the subventricular zone |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276389/ https://www.ncbi.nlm.nih.gov/pubmed/37328883 http://dx.doi.org/10.1186/s40478-023-01586-x |
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