Dataset Information

In Vitro Tracking of Intracellular Metabolism-Derived Cancer Volatiles via Isotope Labeling.

ABSTRACT: Cancer detection relying on the release of volatile biomarkers has been extensively studied, but the individual biochemical processes of the cells from which biogenic volatiles originate have not been thoroughly elucidated to date. Inadequate determination of the metabolic origin of the volatile biomarkers has limited the progress of the scientific and practical applications of volatile biomarkers. To overcome the current limitations, we developed a metabolism tracking approach combining stable isotope labeling and flux analysis of volatiles to trace the intracellular metabolism-derived volatiles and to reveal their relation to cancer metabolic pathways. Specifically, after the 13C labeling of lung cancer cell, the isotopic ratio of whole cellular carbon was measured by nanoscale secondary ion mass spectrometry-based imaging. The kinetic modeling with the time-dependent isotopic ratio determined the period during which cancer cells reach the metabolic steady state, at which time all of the potential volatiles derived from intracellular metabolism were fully enriched isotopically. By measuring the isotopic enrichment of volatiles at the end-stage of isotopic flux, we found that 2-pentadecanone appeared to be derived from the metabolic cascade starting from glucose to fatty acid synthesis. Furthermore, this biosynthetic pathway was determined to be distinct in cancer, as it was upregulated in colon, breast, and pancreatic cancer cells but not in normal cells. The investigation of the metabolic footprint of 2-pentadecanone demonstrates that our novel approach could be applied to trace the metabolic origin of biogenic volatile organic compounds. This analytical strategy represents a potential cutting-edge tool in elucidating the biochemical authenticity of cancer volatiles and further expanding our understanding of the metabolic network of airborne metabolites in vitro.

SUBMITTER: Lee DK

PROVIDER: S-EPMC6107874 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

<i>In Vitro</i> Tracking of Intracellular Metabolism-Derived Cancer Volatiles via Isotope Labeling.

Lee Dong-Kyu DK Na Euiyeon E Park Seongoh S Park Jeong Hill JH Lim Johan J Kwon Sung Won SW

ACS central science 20180803 8

Cancer detection relying on the release of volatile biomarkers has been extensively studied, but the individual biochemical processes of the cells from which biogenic volatiles originate have not been thoroughly elucidated to date. Inadequate determination of the metabolic origin of the volatile biomarkers has limited the progress of the scientific and practical applications of volatile biomarkers. To overcome the current limitations, we developed a metabolism tracking approach combining stable ...[more]

PMID: 30159401

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Project description:BackgroundMetabolic Flux Analysis (MFA) based on isotope labeling experiments (ILEs) is a widely established tool for determining fluxes in metabolic pathways. Isotope labeling networks (ILNs) contain all essential information required to describe the flow of labeled material in an ILE. Whereas recent experimental progress paves the way for high-throughput MFA, large network investigations and exact statistical methods, these developments are still limited by the poor performance of computational routines used for the evaluation and design of ILEs. In this context, the global analysis of ILN topology turns out to be a clue for realizing large speedup factors in all required computational procedures.ResultsWith a strong focus on the speedup of algorithms the topology of ILNs is investigated using graph theoretic concepts and algorithms. A rigorous determination of all cyclic and isomorphic subnetworks, accompanied by the global analysis of ILN connectivity is performed. Particularly, it is proven that ILNs always brake up into a large number of small strongly connected components (SCCs) and, moreover, there are natural isomorphisms between many of these SCCs. All presented techniques are universal, i.e. they do not require special assumptions on the network structure, bidirectionality of fluxes, measurement configuration, or label input. The general results are exemplified with a practically relevant metabolic network which describes the central metabolism of E. coli comprising 10390 isotopomer pools.ConclusionExploiting the topological features of ILNs leads to a significant speedup of all universal algorithms for ILE evaluation. It is proven in theory and exemplified with the E. coli example that a speedup factor of about 1000 compared to standard algorithms is achieved. This widely opens the door for new high performance algorithms suitable for high throughput applications and large ILNs. Moreover, for the first time the global topological analysis of ILNs allows to comprehensively describe and understand the general patterns of label flow in complex networks. This is an invaluable tool for the structural design of new experiments and the interpretation of measured data.

Dataset Information

In Vitro Tracking of Intracellular Metabolism-Derived Cancer Volatiles via Isotope Labeling.

Publications

<i>In Vitro</i> Tracking of Intracellular Metabolism-Derived Cancer Volatiles via Isotope Labeling.

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