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Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes.

ABSTRACT: Cancer cells, like microbes, live in complex metabolic environments. Recent evidence suggests that microbial behavior across metabolic environments is well described by simple empirical growth relationships, or growth laws. Do such empirical growth relationships also exist in cancer cells? To test this question, we develop a high-throughput approach to extract quantitative measurements of cancer cell behaviors in systematically altered metabolic environments. Using this approach, we examine relationships between growth and three frequently studied cancer phenotypes: drug-treatment survival, cell migration, and lactate overflow. Drug-treatment survival follows simple linear growth relationships, which differ quantitatively between chemotherapeutics and EGFR inhibition. Cell migration follows a weak grow-and-go growth relationship, with substantial deviation in some environments. Finally, lactate overflow is mostly decoupled from growth rate and is instead determined by the cells' ability to maintain high sugar uptake rates. Altogether, this work provides a quantitative approach for formulating empirical growth laws of cancer.

SUBMITTER: Kochanowski K

PROVIDER: S-EPMC7877896 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes.

Kochanowski Karl K Sander Timur T Link Hannes H Chang Jeremy J Altschuler Steven J SJ Wu Lani F LF

Cell reports 20210101 3

Cancer cells, like microbes, live in complex metabolic environments. Recent evidence suggests that microbial behavior across metabolic environments is well described by simple empirical growth relationships, or growth laws. Do such empirical growth relationships also exist in cancer cells? To test this question, we develop a high-throughput approach to extract quantitative measurements of cancer cell behaviors in systematically altered metabolic environments. Using this approach, we examine rela ...[more]

PMID: 33472066

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Project description:Plants produce a multitude of metabolites that contribute to their fitness and survival and play a role in local adaptation to environmental conditions. The effects of environmental variation are particularly well studied within the genus Plantago; however, previous studies have largely focused on targeting specific metabolites. Studies exploring metabolome-wide changes are lacking, and the effects of natural environmental variation and herbivory on the metabolomes of plants growing in situ remain unknown. An untargeted metabolomic approach using ultra-high-performance liquid chromatography-mass spectrometry, coupled with variation partitioning, general linear mixed modeling, and network analysis was used to detect differences in metabolic phenotypes of Plantago major in fifteen natural populations across Denmark. Geographic region, distance, habitat type, phenological stage, soil parameters, light levels, and leaf area were investigated for their relative contributions to explaining differences in foliar metabolomes. Herbivory effects were further investigated by comparing metabolomes from damaged and undamaged leaves from each plant. Geographic region explained the greatest number of significant metabolic differences. Soil pH had the second largest effect, followed by habitat and leaf area, while phenological stage had no effect. No evidence of the induction of metabolic features was found between leaves damaged by herbivores compared to undamaged leaves on the same plant. Differences in metabolic phenotypes explained by geographic factors are attributed to genotypic variation and/or unmeasured environmental factors that differ at the regional level in Denmark. A small number of specialized features in the metabolome may be involved in facilitating the success of a widespread species such as Plantago major into such wide range of environmental conditions, although overall resilience in the metabolome was found in response to environmental parameters tested. Untargeted metabolomic approaches have great potential to improve our understanding of how specialized plant metabolites respond to environmental change and assist in adaptation to local conditions.

Dataset Information

Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes.

Publications

Systematic alteration of in vitro metabolic environments reveals empirical growth relationships in cancer cell phenotypes.

Similar Datasets

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