Original Article

Metabolomics

, Volume 9, Issue 2, pp 444-453

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • Kenjiro KamiAffiliated withInstitute for Advanced Biosciences, Keio UniversitySystems Biology Program, Graduate School of Media and Governance, Keio University
  • , Tamaki FujimoriAffiliated withHuman Metabolome Technologies, Inc.
  • , Hajime SatoAffiliated withHuman Metabolome Technologies, Inc.
  • , Mutsuko SatoAffiliated withHuman Metabolome Technologies, Inc.
  • , Hiroyuki YamamotoAffiliated withHuman Metabolome Technologies, Inc.
  • , Yoshiaki OhashiAffiliated withInstitute for Advanced Biosciences, Keio UniversityHuman Metabolome Technologies, Inc. Email author 
  • , Naoyuki SugiyamaAffiliated withInstitute for Advanced Biosciences, Keio University
  • , Yasushi IshihamaAffiliated withGraduate School of Pharmaceutical Sciences, Kyoto University
  • , Hiroko OnozukaAffiliated withNational Cancer Center Hospital East
    • , Atsushi OchiaiAffiliated withNational Cancer Center Hospital East
    • , Hiroyasu EsumiAffiliated withNational Cancer Center Hospital East Email author 
    • , Tomoyoshi SogaAffiliated withInstitute for Advanced Biosciences, Keio UniversitySystems Biology Program, Graduate School of Media and Governance, Keio UniversityHuman Metabolome Technologies, Inc.
    • , Masaru TomitaAffiliated withInstitute for Advanced Biosciences, Keio UniversitySystems Biology Program, Graduate School of Media and Governance, Keio UniversityHuman Metabolome Technologies, Inc.

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.

Keywords

Metabolomics CE-MS Phosphoproteomics Lung cancer Prostate cancer Tumor microenvironment