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Metabolites 2013, 3(4), 1011-1035; doi:10.3390/metabo3041011
Article

Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics

,
,
 and *
Pacific Northwest National Laboratory, 902 Battelle Blvd, Richland, WA 99352, USA
* Author to whom correspondence should be addressed.
Received: 23 August 2013 / Revised: 24 September 2013 / Accepted: 10 October 2013 / Published: 31 October 2013
(This article belongs to the Special Issue NMR-based Metabolomics and Its Application)
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Abstract

NMR metabolomics, consisting of solid state high resolution magic angle spinning (HR-MAS) 1H-NMR, liquid state high resolution 1H-NMR, and principal components analysis (PCA) has been used to study secondary metastatic B16-F10 melanoma in C57BL/6J mouse liver. The melanoma group can be differentiated from its control group by PCA analysis of the estimates of absolute concentrations from liquid state 1H-NMR spectra on liver tissue extracts or by the estimates of absolute peak intensities of metabolites from 1H HR-MAS-NMR data on intact liver tissues. In particular, we found that the estimates of absolute concentrations of glutamate, creatine, fumarate and cholesterol are elevated in the melanoma group as compared to controls, while the estimates of absolute concentrations of succinate, glycine, glucose, and the family of linear lipids including long chain fatty acids, total choline and acyl glycerol are decreased. The ratio of glycerophosphocholine (GPC) to phosphocholine (PCho) is increased by about 1.5 fold in the melanoma group, while the estimate of absolute concentration of total choline is actually lower in melanoma mice. These results suggest the following picture in secondary melanoma metastasis: Linear lipid levels are decreased by beta oxidation in the melanoma group, which contributes to an increase in the synthesis of cholesterol, and also provides an energy source input for TCA cycle. These findings suggest a link between lipid oxidation, the TCA cycle and the hypoxia-inducible factors (HIF) signal pathway in tumor metastases. Thus, this study indicates that the metabolic profile derived from NMR analysis can provide a valuable bio-signature of malignancy and cell hypoxia in metastatic melanoma.
Keywords: 1H HR-MAS; NMR; B16-F10 melanoma; metabolomics; multivariate analysis; PCA 1H HR-MAS; NMR; B16-F10 melanoma; metabolomics; multivariate analysis; PCA
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Feng, J.; Isern, N.G.; Burton, S.D.; Hu, J.Z. Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics. Metabolites 2013, 3, 1011-1035.

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