Cancer metabolism and mass spectrometry-based proteomics.
Cancer metabolism and mass spectrometry-based proteomics.
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DOI：
10.1016/j.canlet.2013.11.003
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发表时间：
2015-01
期刊：
影响因子：
9.7
通讯作者：
Weidong Zhou;L. Liotta;E. Petricoin
中科院分区：
文献类型：
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作者：
Weidong Zhou;L. Liotta;E. Petricoin
人们通过各种工具对癌症代谢进行了广泛的研究，癌细胞中多种代谢重编程的事实已逐渐被揭示。在这篇综述中，我们讨论了使用质谱（MS）技术的一般蛋白质组分析和翻译后修饰分析对癌症代谢的一些贡献。目前的 MS 方法不是跟踪一种或几种代谢酶/途径，而是可以快速识别大量蛋白质并比较它们在不同样本中的表达水平，从而提供癌症代谢的潜在全面图片。胰腺癌细胞的质谱分析支持这样一种假设，即缺氧会促进实体瘤细胞重新编程代谢途径，以最大限度地减少耗氧量。胰腺癌细胞的氧化应激低于正常导管细胞，并且癌细胞适应性地表达较少的抗氧化蛋白，这与癌细胞氧化应激较高的说法相反。另外，MS 分析证实丙酮酸激酶亚型 2 (PKM2) 在癌细胞和正常细胞中均可检测到，这与肿瘤细胞仅表达 PKM2 的报道不同。此外，胰腺癌细胞的质谱分析表明，乳酸脱氢酶-B 在胰腺癌细胞中显着上调，而之前的报道表明，乳酸脱氢酶-A 过度表达，并负责癌细胞中乳酸的产生。最后，质谱分析的结果表明，胰腺癌细胞中的谷氨酰胺分解与胶质母细胞瘤细胞中观察到的不同。
Cancer metabolism has been extensively investigated by various tools, and the fact of diverse metabolic reprogramming in cancer cells has been gradually unveiled. In this review, we discuss some contributions in cancer metabolism by general proteomic analysis and post-translational modification analysis using mass spectrometry (MS) technique. Instead of following one or several metabolic enzymes/pathways, the current MS approach can quickly identify a large number of proteins and compare their expression levels in different samples, providing a potentially comprehensive picture of cancer metabolism. The MS analyses from pancreatic cancer cells support a hypothesis that hypoxia promotes cells in solid tumor to reprogram metabolic pathways in order to minimize the oxygen consumption. The oxidative stress in pancreatic cancer cells is lower than that in normal duct cells, and the cancer cells adaptively express less antioxidant proteins, contrary to claims that oxidative stress is higher in cancer cells. Separately, the MS analyses confirm that pyruvate kinase isoform 2 (PKM2) can be detected in both cancer and normal cells, disagreeing with report that tumor cells express exclusively PKM2. In addition, MS analyses from pancreatic cancer cells demonstrate that lactate dehydrogenase-B is significantly upregulated in pancreatic cancer cells, whereas previous reports show that lactate dehydrogenase-A is overexpressed and is responsible for lactate production in cancer cells. Lastly, the result from MS analysis suggests that the glutaminolysis in pancreatic cancer cells is different from that observed in glioblastoma cells.