Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
Open accessPublished version of a preprint
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.
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Direct measurement of metabolites in human PDAC tumors revealed that some metabolite classes are in low supply and others are increased in abundance.
“Direct measurement of the metabolites in human PDAC tumors revealed classes of metabolites are in low supply for cells within the tumors, and others are increased in abundance193”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [193]
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References 118 · Cited by 588
- Authors
- Sullivan, M. R., Danai, L. V., Lewis, C. A., Chan, S. H., Gui, D. Y., Kunchok, T., Dennstedt, E. A., Vander Heiden, M. G., & Muir, A.
- Affiliations
- Koch Institute for Integrative Cancer Research At MIT (US)
- University of Massachusetts Amherst (US)
- Whitehead Institute for Biomedical Research (US)
- Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, United States
- University of Chicago (US)
- Corresponding author
- Sullivan, Mark R
- Danai, Laura V
- Lewis, Caroline A
- Chan, Sze Ham
- Gui, Dan Y
- Kunchok, Tenzin
- Dennstedt, Emily A
- Muir, Alexander
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2019-04-16
- Volume
- 8
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC6510537
- OpenAlex
- W2950983102
- Cited by
- 588
- References
- 118
- Citations by year
- 2026: 65 · 2025: 95 · 2024: 102 · 2023: 90 · 2022: 68 · 2021: 87 · 2020: 56 · 2019: 24 · 2018: 1
- FWCI
- 18.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Chicago (cc-by)
- Funders
- Koch Institute for Integrative Cancer Research (Koch Institute Graduate Fellowship)
- National Cancer Institute (F32CA210421, R01CA168653, R01CA201276, P30CA1405141, F32CA213810)
- Ludwig Institute for Cancer Research
- Lustgarten Foundation
- Howard Hughes Medical Institute
- Stand Up To Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- tumor microenvironment, extracellular metabolites, tumor interstitial fluid, plasma metabolites, quantitative metabolomics, pancreatic ductal adenocarcinoma, lung adenocarcinoma, autochthonous tumor model, cancer metabolism
- MeSH terms
- Nutrients, Animals, Female, Male, Mice, Inbred C57BL, Neoplasms, Plasma, Extracellular Fluid, Cell Line, Tumor, Metabolomics, Tumor Microenvironment, Heterografts
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