Metabolic Heterogeneity of Brain Tumor Cells of Proneural and Mesenchymal Origin
| Autor: | Kathrin Renner, Katja Dettmer, Marina Kreutz, Martin Proescholdt, Corinna Seliger, Arabel Vollmann-Zwerenz, Anne-Louise Meyer, Nils-Ole Schmidt, Markus J. Riemenschneider, Marsha Merill, Judith Proske, Peter Hau, Martin Uhl, Lisa Rauer, Sylvia Moeckel, Tanja Rothhammer-Hampl, Leon D. Kaulen, Peter J. Oefner, Birgit Jachnik, Verena Leidgens |
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| Rok vydání: | 2022 |
| Předmět: |
Metabolic heterogeneity
Brain Neoplasms Organic Chemistry Mesenchymal stem cell Brain tumor Brain General Medicine Biology medicine.disease Catalysis Metformin Computer Science Applications Inorganic Chemistry Glucose Cell Line Tumor Cancer research medicine Neoplastic Stem Cells Humans glioma metabolism metformin ddc:610 Physical and Theoretical Chemistry Glioblastoma Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 11629 |
| ISSN: | 1422-0067 |
| Popis: | Background: Brain-tumor-initiating cells (BTICs) of proneural and mesenchymal origin contribute to the highly malignant phenotype of glioblastoma (GB) and resistance to current therapies. Methods: BTICs of different subtypes representing tumor heterogeneity were challenged with OXPHOS (oxidative phosphorylation) inhibition to assess the differential effects of metabolic intervention on key resistance features. Results: Whereas mesenchymal BTICs were more invasive, more glycolytic and less responsive to OXPHOS-inhibition, proneural BTICs were less invasive, catabolized glucose more via the pentose phosphate pathways, and responded better to OXPHOS inhibition. Conclusion: Targeting glycolysis may be a promising approach to inhibit highly invasive tumor cells of mesenchymal origin, whereas proneural cells are more responsive to OXPHOS inhibition. Future clinical trials exploring metabolic interventions should account for metabolic heterogeneity of brain tumors to overcome resistance to current treatments. |
| Databáze: | OpenAIRE |
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