Metabotypes of breast cancer cell lines revealed by non-targeted metabolomics
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Date
2017-09
Publication Type
Journal Article
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yes
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Abstract
We present an analysis of intracellular metabolism by
non-targeted, high-throughput metabolomics profiling of 18 breast
cell lines. We profiled >900 putatively annotated metabolite ions
for >100 samples collected under both normoxic and hypoxic
conditions and revealed extensive heterogeneity across all
metabolic pathways and cell lines. Cell line-specific metabolome
profiles dominated over patterns associated with malignancy or
with the clinical nomenclature of breast cancer cells. Such
characteristic metabolome profiles were reproducible across
different laboratories and experiments and exhibited mild to
robust changes with change in experimental conditions. To extract
a functional overview of cell line heterogeneity, we devised an
unsupervised metabotyping procedure that for each pathway
automatically recognized metabolic types from metabolome data and
assigned cell lines. Our procedure provided a condensed yet
global representation of cell line metabolism, revealing the fine
structure of metabolic heterogeneity across all tested pathways
and cell lines. In follow-up experiments on selected pathways, we
confirmed that different metabolic types correlated to
differences in the underlying fluxes and difference sensitivity
to gene knockdown or pharmacological inhibition. Thus, the
identified metabotypes recapitulated functional differences at
the pathway level. Metabotyping provides a powerful compression
of multi-dimensional data that preserves functional information
and serves as a resource for reconciling or understanding
heterogeneous metabolic phenotypes or response to inhibition of
metabolic pathways.
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published
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Book title
Journal / series
Volume
43 (Part B)
Pages / Article No.
173 - 186
Publisher
Elsevier
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Edition / version
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Software
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Date collected
Date created
Subject
Breast cancer; Metabolism; Metabolomics; Typing; Cell line; Modeling
Organisational unit
08839 - Zamboni, Nicola (Tit.-Prof.)
03713 - Sauer, Uwe / Sauer, Uwe
Notes
Funding
156319 - Metabolic types and heterogeneity in breast cancer cell lines (SNF)
Related publications and datasets
Is cited by: https://doi.org/10.3929/ethz-b-000205761