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Tumour metabolism

Feeding the TCA cycle in vivo

Nature Reviews Cancer volume 16, page 198 (2016)Cite this article

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Two papers assess the role of glucose in lung cancer metabolism in vivo.

Because conflicting metabolomics data are often derived from cell culture experiments, Davidson et al. used mouse models of KrasG12D-driven lung tumorigenesis to examine the role of glucose metabolism in vivo. The LA2 model (KrasLA2/+) develops mostly low-grade lung adenomas, KrasLSL-G12D/+Trp53loxP/loxP (KP) mice develop higher-grade metastatic lung tumours and KPS mice develop even more aggressive lung tumours as they are formed from transplantation and outgrowth of KP tumour cells. Mice were infused with [U-13C]glucose and metabolites from lung tumours and normal lung tissue were analysed by gas chromatography–mass spectrometry (GC–MS). The levels of 13C-labelled lactate and pyruvate were similar in the tumours and normal lung tissue from all models, although lactate pools were higher in the KP and KPS tumours, suggesting that these more aggressive tumours may be more glycolytic.

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References

  1. Davidson, S. M. et al. Environment impacts the metabolic dependencies of Ras-driven non-small cell lung cancer. Cell Metabolism 23, 517–528 (2016)

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  2. Hensley, C. T. et al. Metabolic heterogeneity in human lung tumors. Cell 164, 681–694 (2016)

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  1. Gemma K. Alderton
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Alderton, G. Feeding the TCA cycle in vivo. Nat Rev Cancer 16, 198 (2016). https://doi.org/10.1038/nrc.2016.29

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