Analysis of Tumor Metabolism Reveals Mitochondrial Glucose Oxidation in Genetically Diverse Human Glioblastomas in the Mouse Brain In?Vivo

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• 作者：Isaac Marin-Valencia¹ ; ² ; Chendong Yang¹ ; ¹¹ ; Tomoyuki Mashimo³ ; ⁸ ; Steve Cho² ; ⁸ ; Hyeonman Baek³ ; ⁹ ; Xiao-Li Yang³ ; ⁸ ; Kartik  ; N. Rajagopalan¹ ; ¹¹ ; Melissa Maddie³ ; ⁸ ; Vamsidhara Vemireddy³ ; ⁸ ; Zhenze Zhao³ ; ⁸ ; Ling Cai⁴ ; Levi Good¹ ; ² ; Benjamin  ; P. Tu⁴ ; Kimmo  ; J. Hatanpaa⁵ ; ⁸ ; Bruce  ; E. Mickey⁶ ; ⁸ ; José ;   ; M. Maté ; s¹³ ; Juan  ; M. Pascual¹ ; ² ; ⁷ ; Elizabeth  ; A. Maher² ; ³ ; ⁸ ; Craig  ; R. Malloy⁹ ; ¹² ; Ralph  ; J. DeBerardinis¹ ; ¹⁰ ; ¹¹ ; ^{ralph.deberardinis@utsouthwestern.edu} ; Robert  ; M. Bachoo² ; ³ ; ⁸ ; ^{robert.bachoo@utsouthwestern.edu}
• 刊名：Cell Metabolism
• 出版年：2012
• 出版时间：6 June, 2012
• 年：2012
• 卷：15
• 期：6
• 页码：827-837
• 全文大小：1378 K

文摘

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Summary

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.