Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo

Isaac Marin-Valencia, Chendong Yang, Tomoyuki Mashimo, Steve Cho, Hyeonman Baek, Xiao Li Yang, Kartik N. Rajagopalan, Melissa Maddie, Vamsidhara Vemireddy, Zhenze Zhao, Ling Cai, Levi Good, Benjamin P. Tu, Kimmo J. Hatanpaa, Bruce E. Mickey, José M. Matés, Juan M. Pascual, Elizabeth A. Maher, Craig R. Malloy, Ralph J. DeBerardinisRobert M. Bachoo

Research output: Contribution to journalArticlepeer-review

373 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)827-837
Number of pages11
JournalCell Metabolism
Volume15
Issue number6
DOIs
StatePublished - 6 Jun 2012
Externally publishedYes

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