Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
Year: 2019
Type: article
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 developed a quantitative metabolomics method 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. Impact Statement Nutrient availability is an important tumor microenvironmental factor that impacts cancer cell biology; we developed methods to measure nutrients available to tumor cells and characterized factors that influence tumor nutrient availability.
Source: eLife
DOI: 10.7554/elife.44235
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Howard Hughes Medical Institute, Lustgarten Foundation, Ludwig Institute for Cancer Research, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, National Institutes of Health, Stand Up To Cancer, Ludwig Center at Harvard, National Cancer Institute, National Institute of General Medical Sciences
Awards: G2046967885, G3012099682, Understanding cell intrinsic and context dependent metabolic adaptations of cancer cell, Medical Scientist Training Program, Understanding metabolic pathways that support redox homeostasis in cancer, Regulation of glucose metabolism to allow tumor initiation and growth, Analysis of cancer cell metabolism in diverse environmental conditions, Pre-Doctoral Training in Biological Sciences
OpenAlex ID: W2950983102
