What nutrients are actually available inside tumors?
Absolute metabolomics of >118 metabolites shows murine tumor interstitial fluid differs from plasma, and tumor type, location, and diet reshape local nutrient pools.
Source
Quantification of microenvironmental metabolites in murine cancers reveals determinants of tumor nutrient availability
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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.
What they did
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.
What they found
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.
The limits
What it doesn't show
Mouse TIF maps may not match human tumors; centrifugation isolation and model genetics limit direct clinical translation of exact concentrations.
Key terms
- Tumor interstitial fluid (TIF)
- Extracellular fluid that perfuses tumors and supplies nutrients.
- Quantitative metabolomics
- Absolute concentration measurement of many metabolites by LC/MS.
- PDAC / LUAD
- Pancreatic and lung adenocarcinoma murine models studied here.
- Autochthonous model
- Tumor arising in situ (vs transplanted tumor).
- Microenvironment
- Local nutrient and cellular context around cancer cells.
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Primary fluid contrasted with plasma was:
Common questions
How many metabolites?
Absolute concentrations of >118 metabolites.
What fluids compared?
Plasma versus tumor interstitial fluid.
What shaped local nutrients?
Tumor type, anatomical location, and diet.
Human subjects?
No — murine cancer models.
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