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 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 digest In the body, cancer cells can rely on different nutrients than normal cells, and they can use these nutrients in a different way. What cancer cells consume also depends on what is available in their immediate environment. In a tumor, cells grab nutrients from the ‘interstitial’ fluid that surrounds them, but what is present in this liquid may vary within tumors arising in different locations. Understanding what nutrients are ‘on the menu’ in specific tumors would help to target diseased cells while sparing healthy ones, but this knowledge has been difficult to obtain. To investigate this, Sullivan et al. used a technique called mass spectrometry to measure the amounts of 120 nutrients present in the interstitial fluid of mouse pancreas and lung tumors. Different levels of nutrients were found in the two types of tumors, and analyses showed that what was present in the interstitial fluid depended on the type of cancer cells, where the tumor was located, and what the animals ate. This suggests that cancer cells may have different needs because they are limited in what they have access to. It remains to be seen whether the nutrients levels found in mouse tumors are the same as those in humans. Armed with this knowledge, it may then be possible to feed cancer cells grown in the laboratory with the nutrient menu that they would have access to in the body. This could help identify new cancer treatments.