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

• Published in: eLife Vol. 8
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 16.04.2019; eLife Sciences Publications, Ltd
• Subjects: Adenocarcinoma; Animal models; Animals; Biochemistry and Chemical Biology; Cancer; Cancer Biology; Cell Line, Tumor; Extracellular Fluid - chemistry; Female; Fluids; Heterografts - pathology; Laboratories; Lung cancer; Male; mass spectrometry; Medical research; Metabolism; Metabolites; Metabolomics; Mice, Inbred C57BL; microenvironment; Neoplasms - pathology; Nutrient availability; Nutrients; Nutrients - analysis; pancreatic adenocarcinoma; Pancreatic cancer; Pancreatic islet transplantation; Plasma; Plasma - chemistry; Principal components analysis; Statistical analysis; Tumor Microenvironment; Tumors; United States > US; Netherlands; Massachusetts; microenvironment; mouse; pancreatic adenocarcinoma; chemical biology; metabolomics; biochemistry; mass spectrometry; cancer; cancer biology; metabolism
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.44235

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.