Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.
Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.
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DOI：
10.1007/s11306-012-0452-2
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发表时间：
2013-04
期刊：
影响因子：
3.6
通讯作者：
Tomita, Masaru
中科院分区：
文献类型：
--
作者：
Kami, Kenjiro;Fujimori, Tamaki;Sato, Hajime;Sato, Mutsuko;Yamamoto, Hiroyuki;Ohashi, Yoshiaki;Sugiyama, Naoyuki;Ishihama, Yasushi;Onozuka, Hiroko;Ochiai, Atsushi;Esumi, Hiroyasu;Soga, Tomoyoshi;Tomita, Masaru
肿瘤细胞的代谢微环境受到致癌信号传导和组织特异性代谢需求、血液供应和酶表达的影响。为了阐明肿瘤特异性代谢，我们使用毛细管电泳飞行时间质谱 (CE-TOFMS) 比较了从 9 名肺癌患者和 7 名前列腺癌患者手术切除的正常组织和肿瘤组织的代谢组学。还对参与中心碳代谢的酶的磷酸化水平进行了定量。肺和前列腺组织的代谢组学谱分别包含 114 种和 86 种代谢物，这些谱不仅可以很好地区分肿瘤与正常组织，还可以区分肺癌中的鳞状细胞癌与其他肿瘤类型以及前列腺癌中的低分化肿瘤与中分化肿瘤。大多数氨基酸，尤其是支链氨基酸的浓度在肿瘤组织中显着较高，与器官类型无关，但必需氨基酸在低分化前列腺癌中的浓度特别高于中分化前列腺癌。器官依赖性差异在糖酵解和三羧酸循环中间体的水平以及相关的能量状态方面是显着的。肺肿瘤中乳酸浓度显着升高，磷酸果糖激酶和丙酮酸激酶的活化磷酸化水平升高，证实了糖酵解过度活跃。我们强调了基于 CE-TOFMS 的代谢组学与磷酸化酶分析相结合在了解组织特异性肿瘤微环境方面的潜力，这可能会导致开发更有效和特异性的抗癌疗法。本文的在线版本 (doi:10.1007/s11306-012-0452-2) 包含补充材料，可供授权用户使用。
Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics. The online version of this article (doi:10.1007/s11306-012-0452-2) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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通讯作者：
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