Journal
METABOLOMICS
Volume 9, Issue 2, Pages 444-453Publisher
SPRINGER
DOI: 10.1007/s11306-012-0452-2
Keywords
Metabolomics; CE-MS; Phosphoproteomics; Lung cancer; Prostate cancer; Tumor microenvironment
Categories
Funding
- Ministry of Health, Labour and Welfare
- Global COE Program
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Yamagata prefectural government
- City of Tsuruoka
- Grants-in-Aid for Scientific Research [24116513, 22134007, 24659017, 23134507] Funding Source: KAKEN
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available