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

作者：Marin Valencia Isaac; Yang Chendong; Mashimo Tomoyuki; Cho Steve; Baek Hyeonman; Yang Xiao Li; Rajagopalan Kartik N; Maddie Melissa; Vemireddy Vamsidhara; Zhao Zhenze; Cai Ling; Good Levi; Tu Benjamin P; Hatanpaa Kimmo J; Mickey Bruce E; Mates Jose M; Pascual Juan M; Maher Elizabeth A; Malloy Craig R; DeBerardinis Ralph J^*; Bachoo Robert M

来源：Cell Metabolism, 2012, 15(6): 827-837.

DOI：10.1016/j.cmet.2012.05.001

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 C-13-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.

• 出版日期2012-6-6