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定量分析小鼠癌症中的微环境代谢物，揭示肿瘤营养供应的决定因素。

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

机构信息

Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.

Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, United States.

出版信息

Elife. 2019 Apr 16;8:e44235. doi: 10.7554/eLife.44235.

DOI:10.7554/eLife.44235
PMID:30990168
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6510537/
Abstract

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.

摘要

癌细胞代谢受到微环境因素的强烈影响，包括营养物质的可利用性。因此，了解微环境中营养物质的水平对于理解肿瘤代谢至关重要。为了测量肿瘤可用的细胞外营养物质水平，我们利用定量代谢组学方法测量了血浆和肿瘤间质液（灌注肿瘤的细胞外液）中超过 118 种代谢物的绝对浓度。比较肿瘤间质液和血浆中的营养物质水平表明，肿瘤可用的营养物质与循环中存在的营养物质不同。此外，通过比较鼠胰腺和肺腺癌的同源和移植模型的间质液营养物质水平，我们发现肿瘤类型、解剖位置和动物饮食影响局部营养物质的可利用性。这些数据全面描述了广泛使用的肺和胰腺癌模型中肿瘤微环境中的营养物质，并确定了影响肿瘤中代谢物水平的因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/d5eca2484a49/elife-44235-fig6-figsupp2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/1c527c2524fc/elife-44235-fig2-figsupp6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/d2465a71a5b0/elife-44235-fig2-figsupp7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/2c2747627e00/elife-44235-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/f5fcd2b755c2/elife-44235-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/f5206de4698c/elife-44235-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/ec0a603f002d/elife-44235-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/0dadf8495468/elife-44235-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/315860908aeb/elife-44235-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/952f2c3131d9/elife-44235-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/0b7a3040093c/elife-44235-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/296d4b1fa368/elife-44235-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/2b28b32fdff0/elife-44235-fig5-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/928e715811ef/elife-44235-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/be51dcfaac02/elife-44235-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/053c/6510537/d5eca2484a49/elife-44235-fig6-figsupp2.jpg

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本文引用的文献

[1]
Increased Serine Synthesis Provides an Advantage for Tumors Arising in Tissues Where Serine Levels Are Limiting.

Cell Metab. 2019-3-21

[2]
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Trends Cancer. 2018-10

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Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies.

Dis Model Mech. 2018-8-7

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