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Elife. 2019 Apr 16;8. pii: e44235. doi: 10.7554/eLife.44235.

Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability.

Author information

1
Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.
2
Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, United States.
3
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, United States.
4
Dana-Farber Cancer Institute, Boston, United States.
5
Ben May Department for Cancer Research, University of Chicago, Chicago, United States.

Abstract

Cancer cell metabolism is heavily influenced by microenvironmental factors, including nutrient availability. Therefore, knowledge of microenvironmental nutrient levels is essential to understand tumor metabolism. To measure the extracellular nutrient levels available to tumors, we utilized quantitative metabolomics methods to measure the absolute concentrations of >118 metabolites in plasma and tumor interstitial fluid, the extracellular fluid that perfuses tumors. Comparison of nutrient levels in tumor interstitial fluid and plasma revealed that the nutrients available to tumors differ from those present in circulation. Further, by comparing interstitial fluid nutrient levels between autochthonous and transplant models of murine pancreatic and lung adenocarcinoma, we found that tumor type, anatomical location and animal diet affect local nutrient availability. These data provide a comprehensive characterization of the nutrients present in the tumor microenvironment of widely used models of lung and pancreatic cancer and identify factors that influence metabolite levels in tumors.

KEYWORDS:

biochemistry; cancer; cancer biology; chemical biology; mass spectrometry; metabolism; metabolomics; microenvironment; mouse; pancreatic adenocarcinoma

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