Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics.
Studies of Secondary Melanoma on C57BL/6J Mouse Liver Using 1H NMR Metabolomics.
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DOI：
10.3390/metabo3041011
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发表时间：
2013-10-31
期刊：
影响因子：
4.1
通讯作者：
Hu JZ
中科院分区：
文献类型：
--
作者：
Feng J;Isern NG;Burton SD;Hu JZ
NMR 代谢组学由固态高分辨率魔角旋转 (HR-MAS) 1H-NMR、液态高分辨率 1H-NMR 和主成分分析 (PCA) 组成，已用于研究 C57BL/6J 小鼠肝脏中的继发性转移性 B16-F10 黑色素瘤。通过对肝组织提取物的液态 1H-NMR 光谱的绝对浓度估计进行 PCA 分析，或通过对完整肝组织的 1H HR-MAS-NMR 数据估计代谢物的绝对峰强度，可以将黑色素瘤组与其对照组区分开来。特别是，我们发现，与对照组相比，黑色素瘤组中谷氨酸、肌酸、富马酸和胆固醇的绝对浓度估计值升高，而琥珀酸、甘氨酸、葡萄糖和线性脂质家族（包括长链脂肪酸、总胆碱和酰基甘油）的绝对浓度估计值降低。黑色素瘤组中甘油磷酸胆碱 (GPC) 与磷酸胆碱 (PCho) 的比率增加了约 1.5 倍，而黑色素瘤小鼠中总胆碱绝对浓度的估计值实际上较低。这些结果提示了继发性黑色素瘤转移中的以下情况：黑色素瘤组中的β氧化导致线性脂质水平降低，这有助于胆固醇合成的增加，并且还为TCA循环提供能量来源输入。这些发现表明肿瘤转移中脂质氧化、TCA 循环和缺氧诱导因子 (HIF) 信号通路之间存在联系。因此，这项研究表明，核磁共振分析得出的代谢谱可以提供转移性黑色素瘤中恶性肿瘤和细胞缺氧的有价值的生物特征。
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.