1H NMR metabolomics identification of markers of hypoxia-induced metabolic shifts in a breast cancer model system

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1H NMR metabolomics identification of markers of hypoxia-induced metabolic shifts in a breast cancer model system


Abstract Hypoxia can promote invasive behavior in cancer cells and alters the response to therapeutic intervention as a result of changes in the expression many genes, including genes involved in intermediary metabolism. Although metabolomics technologies are capable of simultaneously measuring a wide range of metabolites in an untargeted manner, these methods have been relatively under utilized in the study of cancer cell responses to hypoxia. Thus, 1H NMR metabolomics was used to examine the effects of hypoxia in the MDA-MB-231 human breast cancer cell line, both in vitro and in vivo. Cell cultures were compared with respect to their metabolic responses during growth under either hypoxic (1% O2) or normoxic conditions. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify a set of metabolites that were responsive to hypoxia. Via intracardiac administration, MDA-MB-231 cells were also used to generate widespread metastatic disease in immuno-compromised mice. Serum metabolite analysis was conducted to compare animals with and without a large tumor burden. Intriguingly, using a cross-plot of the OPLS loadings, both the in vitro and in vivo samples yielded a subset of metabolites that were significantly altered by hypoxia. These included primarily energy metabolites and amino acids, indicative of known alterations in energy metabolism, and possibly protein synthesis or catabolism. The results suggest that the metabolite pattern identified might prove useful as a marker for intra-tumoral hypoxia.

• Content Type Journal Article
• Pages 1-9
• DOI 10.1007/s10858-011-9486-4
• Authors
  • Aalim M. Weljie, Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, AB T2N 1N4, Canada
  • Alla Bondareva, Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, Calgary, AB Canada
  • Ping Zang, Department of Chemistry, University of Calgary, Calgary, AB T2N 1N4, Canada
  • Frank R. Jirik, Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, Calgary, AB Canada

• • Journal Journal of Biomolecular NMR
  • Online ISSN 1573-5001
  • Print ISSN 0925-2738

Source: Journal of Biomolecular NMR