Semi-quantitative analyses of metabolic systems of human colon cancer metastatic xenografts in livers of superimmunodeficient NOG mice

Akiko Kubo, Mitsuyo Ohmura, Masatoshi Wakui, Takahiro Harada, Shigeki Kajihara, Kiyoshi Ogawa, Hiroshi Suemizu, Masato Nakamura, Mitsutoshi Setou, Makoto Suematsu

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Analyses of energy metabolism in human cancer have been difficult because of rapid turnover of the metabolites and difficulties in reducing time for collecting clinical samples under surgical procedures. Utilization of xenograft transplantation of human-derived colon cancer HCT116 cells in spleens of superimmunodeficient NOD/SCID/IL-2Rγnull (NOG) mice led us to establish an experimental model of hepatic micrometastasis of the solid tumor, whereby analyses of the tissue sections collected by snap-frozen procedures through newly developed microscopic imaging mass spectrometry (MIMS) revealed distinct spatial distribution of a variety of metabolites. To perform intergroup comparison of the signal intensities of metabolites among different tissue sections collected from mice in fed states, we combined matrix-assisted laser desorption/ionization time-of-flight imaging mass spectrometry (MALDI-TOF-IMS) and capillary electrophoresis-mass spectrometry (CE-MS), to determine the apparent contents of individual metabolites in serial tissue sections. The results indicated significant elevation of ATP and energy charge in both metastases and the parenchyma of the tumor-bearing livers. To note were significant increases in UDP-N-acetyl hexosamines, and reduced and oxidized forms of glutathione in the metastatic foci versus the liver parenchyma. These findings thus provided a potentially important method for characterizing the properties of metabolic systems of human-derived cancer and the host tissues in vivo.

Original languageEnglish
Pages (from-to)1895-1904
Number of pages10
JournalAnalytical and bioanalytical chemistry
Volume400
Issue number7
DOIs
Publication statusPublished - 2011 Jun

Keywords

  • Capillary electrophoresis-mass spectrometry (CE-MS)
  • Glycoprotein biosynthesis
  • Imaging mass spectrometry (IMS)
  • Matrix-assisted laser desorption/ionization (MALDI)
  • Metabolome
  • Tumor-bearing liver

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry

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