caa a22 4500 44532483X CHVBK 20180317142716.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s10858-011-9486-4 doi (NATIONALLICENCE)springer-10.1007/s10858-011-9486-4 1H NMR metabolomics identification of markers of hypoxia-induced metabolic shifts in a breast cancer model system [Elektronische Daten] [Aalim Weljie, Alla Bondareva, Ping Zang, Frank Jirik] 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. Springer Science+Business Media B.V., 2011 Metabolomics nationallicence 1H NMR spectroscopy nationallicence Hypoxia nationallicence Glycolysis nationallicence Breast cancer nationallicence Chemometrics nationallicence OPLS-DA nationallicence Tumor xenograft nationallicence HIF : Hypoxia inducible factor nationallicence MCT : Monocarboxylate transporter nationallicence MDA-MB-231-Luc2 : MDA-MB-231 Luciferase nationallicence OPLS-DA : Orthogonal partial least squares discriminant analysis nationallicence PCA : Principal component analysis nationallicence VIP : Variable influence on projection nationallicence Weljie Aalim Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, T2N 1N4, Calgary, AB, Canada aut Bondareva Alla Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, Calgary, AB, Canada aut Zang Ping Department of Chemistry, University of Calgary, T2N 1N4, Calgary, AB, Canada aut Jirik Frank Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, Calgary, AB, Canada aut Journal of Biomolecular NMR Springer Netherlands 49/3-4(2011-04-01), 185-193 0925-2738 49:3-4<185 2011 49 10858 https://doi.org/10.1007/s10858-011-9486-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10858-011-9486-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Weljie Aalim Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, T2N 1N4, Calgary, AB, Canada aut NATIONALLICENCE 700 1- Bondareva Alla Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, Calgary, AB, Canada aut NATIONALLICENCE 700 1- Zang Ping Department of Chemistry, University of Calgary, T2N 1N4, Calgary, AB, Canada aut NATIONALLICENCE 700 1- Jirik Frank Department of Biochemistry and Molecular Biology, McCaig Institute for Bone and Joint Health, Calgary, AB, Canada aut NATIONALLICENCE 773 0- Journal of Biomolecular NMR Springer Netherlands 49/3-4(2011-04-01), 185-193 0925-2738 49:3-4<185 2011 49 10858 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer