Metabolism
What nutrients are actually available inside tumors?
Open access · cc by · source: Europe PMC
Absolute metabolomics of >118 metabolites shows murine tumor interstitial fluid differs from plasma, and tumor type, location, and diet reshape local nutrient pools.
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What nutrients are actually available inside tumors?
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>118 metabolite concentrations measured in plasma and TIF.
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.
Method quantified >118 nutrients using standards and isotope dilution.
To do so, we have utilized a quantitative mass spectrometry-based approach using both external standards and stable isotope dilution of a library of carbon labeled metabolites to determine the concentration of >118 nutrients in biological fluids.
Key findings
Nutrients available in TIF differ from circulating plasma. Comparing models showed tumor type, anatomical location, and animal diet affect local nutrient availability; diet changes appear in TIF, while a Keap1 mutation in LUAD had a smaller microenvironment effect.
Methodology
Used quantitative mass spectrometry with standards/isotope dilution to measure absolute concentrations of >118 metabolites in plasma and tumor interstitial fluid (TIF) from autochthonous and transplant murine lung and pancreatic adenocarcinoma models.
Limitations
Mouse TIF maps may not match human tumors; centrifugation isolation and model genetics limit direct clinical translation of exact concentrations.
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