Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
- Massachusetts Institute of Technology, United States
- University of 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.
Data availability
Source data files detailing the concentrations of each metabolite in each sample are included for all figures. We have also deposited this information and the raw mass spectra in Metabolomics Workbench (http://www.metabolomicsworkbench.org/) as project ID: PR000750.
Article and author information
Author details
Matthew G Vander Heiden
Funding
National Cancer Institute (R01CA168653)
- Matthew G Vander Heiden
National Cancer Institute (F32CA210421)
- Laura V Danai
- Alexander Muir
Stand Up To Cancer
- Mark R Sullivan
- Laura V Danai
- Dan Y Gui
- Matthew G Vander Heiden
- Alexander Muir
Howard Hughes Medical Institute
- Mark R Sullivan
- Laura V Danai
- Dan Y Gui
- Matthew G Vander Heiden
- Alexander Muir
Ludwig Institute for Cancer Research
- Mark R Sullivan
- Laura V Danai
- Dan Y Gui
- Matthew G Vander Heiden
- Alexander Muir
Lustgarten Foundation
- Mark R Sullivan
- Laura V Danai
- Dan Y Gui
- Matthew G Vander Heiden
- Alexander Muir
Koch Institute for Integrative Cancer Research (Koch Institute Graduate Fellowship)
- Mark R Sullivan
National Cancer Institute (R01CA201276)
- Matthew G Vander Heiden
National Cancer Institute (P30CA1405141)
- Matthew G Vander Heiden
National Cancer Institute (F32CA213810)
- Laura V Danai
- Alexander Muir
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ralph DeBerardinis, UT Southwestern Medical Center, United States
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals. All animals experiments were performed using protocols (#1115-110-18) that were approved by the MIT Committee on Animal Care (IACUC). All surgeries were performed using isoflurane anesthesia administered by vaporizer and every effort was made to minimize suffering.
Version history
- Received: December 10, 2018
- Accepted: April 4, 2019
- Accepted Manuscript published: April 16, 2019 (version 1)
- Version of Record published: May 10, 2019 (version 2)
Copyright
© 2019, Sullivan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
eLife 8:e44235.
https://doi.org/10.7554/eLife.44235
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