title: Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.
abstract: 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.
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata Japan ; Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kami
authors.forename: Tamaki
authors.initials: T
authors.lastname: Fujimori
authors.forename: Hajime
authors.initials: H
authors.lastname: Sato
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohashi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sugiyama
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishihama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Onozuka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Esumi
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
keywords: CE-MS; Lung cancer; Metabolomics; Phosphoproteomics; Prostate cancer; Tumor microenvironment
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