Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model
| العنوان: | Integrated analysis identifies different metabolic signatures for tumor-initiating cells in a murine glioblastoma model |
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| المؤلفون: | Masatoshi Kusuhara, Kazunari Yoshida, Kenichi Urakami, Satoru Osuka, Yusuke Kobayashi, Sachiko Yamada, Oltea Sampetrean, Jun Okubo, Shunsuke Shibao, Isako Saga, Satoshi Fujita, Hideyuki Saya |
| المصدر: | Neuro-Oncology. 16:1048-1056 |
| بيانات النشر: | Oxford University Press (OUP), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Cancer Research, Biology, Malignant transformation, Mice, In vivo, Glioma, Tumor Cells, Cultured, medicine, Animals, Humans, Glycolysis, Brain Neoplasms, Cell Differentiation, Metabolism, medicine.disease, Neural stem cell, Disease Models, Animal, Cell Transformation, Neoplastic, Oncology, Biochemistry, Basic and Translational Investigations, Neoplastic Stem Cells, Cancer research, Neurology (clinical), Glioblastoma, Energy source, Pyruvate kinase |
| الوصف: | Background. The metabolic preference of malignant glioma for glycolysis as an energy source is a potential therapeutic target. As a result of the cellular heterogeneity of these tumors, however, the relation between glycolytic preference, tumor formation, and tumor cell clonogenicity has remained unknown. To address this issue, we analyzed the metabolic profiles of isogenic glioma-initiating cells (GICs) in a mouse model. Methods. GICs were established by overexpression of H-Ras V12 in Ink4a/Arf‐null neural stem cells. Subpopulations of these cells were obtained by single-cell cloning, and clones differing in extracellular acidification potential were assessed for metabolic characteristics. Tumors formed after intracranial implantation of these clones in mice were examined for pathological features of glioma and expression of glycolytic enzymes. Results. Malignant transformation of neural stem cells resulted in a shift in metabolism characterized by an increase in lactic acid production. However, isogenic clonal populations of GICs manifested pronounced differences in glucose and oxygen consumption, lactate production, and nucleoside levels. These differences were paralleled by differential expression of glycolytic enzymes such as hexokinase 2 and pyruvate kinase M2, with this differential expression also being evident in tumors formed by these clones in vivo. Conclusions. The metabolic characteristics of glioma cells appear early during malignant transformation and persist until the late stages of tumor formation. Even isogenic clones may be heterogeneous in terms of metabolic features, however, suggesting that a more detailed understanding of the metabolic profile of glioma is imperative for effective therapeutic targeting. |
| تدمد: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/nou096 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7f085efa1093b2e0cbf9f8e19138dd09 https://doi.org/10.1093/neuonc/nou096 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7f085efa1093b2e0cbf9f8e19138dd09 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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| DOI: | 10.1093/neuonc/nou096 |