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

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 quantitat...

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Autores principales: Sullivan, Mark R, Danai, Laura V, Lewis, Caroline A, Chan, Sze Ham, Gui, Dan Y, Kunchok, Tenzin, Dennstedt, Emily A, Vander Heiden, Matthew G, Muir, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510537/
https://www.ncbi.nlm.nih.gov/pubmed/30990168
http://dx.doi.org/10.7554/eLife.44235
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author Sullivan, Mark R
Danai, Laura V
Lewis, Caroline A
Chan, Sze Ham
Gui, Dan Y
Kunchok, Tenzin
Dennstedt, Emily A
Vander Heiden, Matthew G
Muir, Alexander
author_facet Sullivan, Mark R
Danai, Laura V
Lewis, Caroline A
Chan, Sze Ham
Gui, Dan Y
Kunchok, Tenzin
Dennstedt, Emily A
Vander Heiden, Matthew G
Muir, Alexander
author_sort Sullivan, Mark R
collection PubMed
description 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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spelling pubmed-65105372019-05-13 Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability Sullivan, Mark R Danai, Laura V Lewis, Caroline A Chan, Sze Ham Gui, Dan Y Kunchok, Tenzin Dennstedt, Emily A Vander Heiden, Matthew G Muir, Alexander eLife Biochemistry and Chemical Biology 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. eLife Sciences Publications, Ltd 2019-04-16 /pmc/articles/PMC6510537/ /pubmed/30990168 http://dx.doi.org/10.7554/eLife.44235 Text en © 2019, Sullivan et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Sullivan, Mark R
Danai, Laura V
Lewis, Caroline A
Chan, Sze Ham
Gui, Dan Y
Kunchok, Tenzin
Dennstedt, Emily A
Vander Heiden, Matthew G
Muir, Alexander
Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
title Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
title_full Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
title_fullStr Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
title_full_unstemmed Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
title_short Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
title_sort quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510537/
https://www.ncbi.nlm.nih.gov/pubmed/30990168
http://dx.doi.org/10.7554/eLife.44235
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