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首页> 外文期刊>Cell metabolism >Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo
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Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo

机译：肿瘤代谢分析揭示了小鼠脑内遗传多样的人类胶质母细胞瘤中线粒体葡萄糖氧化

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Dysregulated metabolism is a hallmark of cancer cell lines, but little is known about the fate of glucose and other nutrients in tumors growing in their native microenvironment. To study tumor metabolism in vivo, we used an orthotopic mouse model of primary human glioblastoma (GBM). We infused 13C-labeled nutrients into mice bearing three independent GBM lines, each with a distinct set of mutations. All three lines displayed glycolysis, as expected for aggressive tumors. They also displayed unexpected metabolic complexity, oxidizing glucose via pyruvate dehydrogenase and the citric acid cycle, and using glucose to supply anaplerosis and other biosynthetic activities. Comparing the tumors to surrounding brain revealed obvious metabolic differences, notably the accumulation of a large glutamine pool within the tumors. Many of these same activities were conserved in cells cultured ex vivo from the tumors. Thus GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo.
机译：代谢失调是癌细胞系的标志，但对于在其天然微环境中生长的肿瘤中葡萄糖和其他营养素的命运知之甚少。为了研究体内的肿瘤代谢，我们使用了原代人胶质母细胞瘤（GBM）的原位小鼠模型。我们向带有三个独立GBM系的小鼠中注入了13C标记的营养素，每个系均具有一组独特的突变。如对侵袭性肿瘤所期望的，所有三个系均显示出糖酵解。他们还表现出出乎意料的代谢复杂性，通过丙酮酸脱氢酶和柠檬酸循环氧化葡萄糖，并利用葡萄糖提供抗衰老和其他生物合成活动。将肿瘤与周围的大脑进行比较显示出明显的代谢差异，特别是肿瘤内大量谷氨酰胺的积累。这些相同的活性中有许多在肿瘤离体培养的细胞中得以保留。因此，GBM细胞在体内侵袭性肿瘤生长期间利用线粒体葡萄糖氧化。

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