Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry

Kenjiro Kami, Tamaki Fujimori, Hajime Sato, Mutsuko Sato, Hiroyuki Yamamoto, Yoshiaki Ohashi, Naoyuki Sugiyama, Yasushi Ishihama, Hiroko Onozuka, Atsushi Ochiai, Hiroyasu Esumi, Tomoyoshi Soga, Masaru Tomita

Research output: Contribution to journalArticle

87 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)444-453
Number of pages10
JournalMetabolomics
Volume9
Issue number2
DOIs
Publication statusPublished - 2013

Fingerprint

Capillary electrophoresis
Metabolomics
Capillary Electrophoresis
Mass spectrometry
Tumors
Prostate
Mass Spectrometry
Tissue
Lung
Neoplasms
Prostatic Neoplasms
Tumor Microenvironment
Phosphorylation
Enzymes
Metabolism
Cellular Microenvironment
Phosphofructokinases
Branched Chain Amino Acids
Pyruvate Kinase
Essential Amino Acids

Keywords

  • CE-MS
  • Lung cancer
  • Metabolomics
  • Phosphoproteomics
  • Prostate cancer
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry. / 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.

In: Metabolomics, Vol. 9, No. 2, 2013, p. 444-453.

Research output: Contribution to journalArticle

Kami, K, Fujimori, T, Sato, H, Sato, M, Yamamoto, H, Ohashi, Y, Sugiyama, N, Ishihama, Y, Onozuka, H, Ochiai, A, Esumi, H, Soga, T & Tomita, M 2013, 'Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry', Metabolomics, vol. 9, no. 2, pp. 444-453. https://doi.org/10.1007/s11306-012-0452-2
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. / Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry. In: Metabolomics. 2013 ; Vol. 9, No. 2. pp. 444-453.
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