Abstract

Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using 13C-NMR analysis of brain tumors resected from patients during infusion of 13C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-13C]acetate and can do so while simultaneously oxidizing [1,6-13C]glucose. The tumors do not oxidize [U-13C]glutamine. In vivo oxidation of [1,2-13C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth.

Original languageEnglish (US)
Pages (from-to)1603-1614
Number of pages12
JournalCell
Volume159
Issue number7
DOIs
StatePublished - Dec 18 2014

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Glioblastoma
Brain Neoplasms
Energy Metabolism
Tumors
Brain
Acetates
Neoplasm Metastasis
Substrates
Glucose
Citric Acid Cycle
Acetate-CoA Ligase
Acetyl Coenzyme A
Oxidation
Glutamine
Carbon
Phenotype
Nuclear magnetic resonance
Survival
Enzymes
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. / Mashimo, Tomoyuki; Pichumani, Kumar; Vemireddy, Vamsidhara; Hatanpaa, Kimmo J.; Singh, Dinesh Kumar; Sirasanagandla, Shyam; Nannepaga, Suraj; Piccirillo, Sara G.; Kovacs, Zoltan; Foong, Chan; Huang, Zhiguang; Barnett, Samuel; Mickey, Bruce E.; Deberardinis, Ralph J.; Tu, Benjamin P.; Maher, Elizabeth A.; Bachoo, Robert M.

In: Cell, Vol. 159, No. 7, 18.12.2014, p. 1603-1614.

Research output: Contribution to journalArticle

Mashimo T, Pichumani K, Vemireddy V, Hatanpaa KJ, Singh DK, Sirasanagandla S et al. Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. Cell. 2014 Dec 18;159(7):1603-1614. https://doi.org/10.1016/j.cell.2014.11.025
Mashimo, Tomoyuki ; Pichumani, Kumar ; Vemireddy, Vamsidhara ; Hatanpaa, Kimmo J. ; Singh, Dinesh Kumar ; Sirasanagandla, Shyam ; Nannepaga, Suraj ; Piccirillo, Sara G. ; Kovacs, Zoltan ; Foong, Chan ; Huang, Zhiguang ; Barnett, Samuel ; Mickey, Bruce E. ; Deberardinis, Ralph J. ; Tu, Benjamin P. ; Maher, Elizabeth A. ; Bachoo, Robert M. / Acetate is a bioenergetic substrate for human glioblastoma and brain metastases. In: Cell. 2014 ; Vol. 159, No. 7. pp. 1603-1614.
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