RT Journal Article
SR Electronic
T1 Quantification of microenvironmental metabolites in murine cancer models reveals determinants of tumor nutrient availability
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 492652
DO 10.1101/492652
A1 Mark R Sullivan
A1 Laura V Danai
A1 Caroline A Lewis
A1 Sze Ham Chan
A1 Dan Y Gui
A1 Tenzin Kunchok
A1 Emily A Dennstedt
A1 Matthew G Vander Heiden
A1 Alexander Muir
YR 2019
UL http://biorxiv.org/content/early/2019/01/03/492652.abstract
AB 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.