Research Project
Grant-in-Aid for Scientific Research (C)
Liver failure through disseminated metastasis through portal circulation is one of the most serious clinical complications of the colon cancer, although mechanisms for maintaining the organ homeostasis of energy metabolism under the tumor-bearing conditions remain largely unknown. We aimed to dissect such mechanisms by establishing an experimental model of the liver metastasis of human colon cancer using the superimmunodeficient NOD/scid/Y^null (NOG) mice that allow immunological tolerance for the growth of mutant GFP (venus)-expressing HCT116 colon cancer cells in the liver. The metastatic cancer cells in the liver were successfully visualized through a newly developed fluorescence confocal microscopy. This microscopy made it possible to achieve high resolution images of the tumor microcirculation with little phototoxicity. The presented NOG mouse model with Venus transfected colon cancer cells stands for the portal metastatic route and enables us to perform dynamic observation of ear … More ly events in metastasis.We collected the hepatocytes from the livers through the conventional collagenase perfusion method. The isolated hepatocyte(control)and venus-expressing tumor-bearing cells by FACS were incubated with ^<13>C13_6-glucose-, ^<13>C_3-pyruvate-, or ^<15>N_2-glutamine-contained medium, and the differences in metabolic profiling of hepatocytes between the control and tumor-bearing cells were examined. The metabolome analysis of these cells using CE/MS led us to reveal remarkable alterations in metabolites in glycolysis, TCA cycle, pentose phosphate pathway, and profiles of amino acids. The challenge test using ^<15>N-labelled glutamine revealed that hepatocytes from the tumor-bearing liver accelerate incorporation of the amino acid to nucleotides for DNA synthesis; the event matched histological observation showing activation of the proliferation marker such as PCNA.The results collectively suggest that tumor-bearing conditions trigger metabolic remodeling of the hepatocytes that might satisfy metabolic demand of the cells for DNA synthesis and post-translational protein modification but compromise the ability to deliver glucose through gluconeogenesis. Less
All 2008 2007
All Journal Article (13 results) (of which Peer Reviewed: 6 results) Presentation (7 results)
Tansplantation 85(3)
Pages: 378-385
Hepatology 47(1)
Pages: 143-152
肝、胆、膵 56(1)
Pages: 127-132
Tranplantation 85(3)
Transplantation 85(3)
肝・胆・膵 56(1)
手術 61(6)
Pages: 701-706
American Journal of Transplantation 7(9)
Pages: 2204-2207
American.Journal of Transplantation 7(9)
