2007 Fiscal Year Final Research Report Summary
Intravital microcircular observation and metabolome analysis of the liver bearing human-derived metastatic colon cancer metastasis in the superimmunodeficient NOG mice
| Project/Area Number |
18591524
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Keio University |
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Principal Investigator |
SHIMZAU Motohide Keio University, School of medicine, Professor (70124948)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Live / Metastasis / Metabolome / Immunodeficient mouse |
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| Research Abstract |
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
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Author(s)
Hasegawa Y, Kato Y, Kaneko MK, Ogasawara S, Shimazu M, Tanabe M, Kawachi S, Obara H, Shinoda M, Kitagawa Y, Narimatsu H, Kitaiima M
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Journal Title
Tansplantation 85(3)
Pages: 378-385
Description
「研究成果報告書概要(和文)」より
Peer Reviewed
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[Journal Article] 糖代謝および脂質代謝異常と肝臓 脂肪肝と肝移植2008
Author(s)
田辺 稔, 河地 茂行, 尾原 秀明, 篠田 昌宏, 渕本 康史, 星野 健, 島津 元秀, 北島 政樹, 柴田 理恵, 坂元 亨宇, 森川 康英, 北川 雄光
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Journal Title
肝、胆、膵 56(1)
Pages: 127-132
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Neutralization of blood group A-antigen by a novel anti-A antibody : overcoming ABO-incompatible solid-organ transplantation2008
Author(s)
Hasegawa, Y, Kato, Y, Kaneko, MK, Ogasawara, S, Shimazu, M, Tanabe, M, Kawachi, S, Obara, H, Shinoda, M, Kitagawa, Y, Narimatsu, H, Kitajima, M
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Journal Title
Tranplantation 85(3)
Pages: 378-385
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Present status of ABO-incompatible living donor liver transplantation in Japan2008
Author(s)
Egawa, H, Teramukai, S, Haga, H, Tanabe, M, Fukushima, M, Shimazu, M
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Journal Title
Hepatology 47(1)
Pages: 143-152
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Discontinuation of living donor liver transplantation for PSC due to his tological abnormalities in intraoperative donor liver biopsy2007
Author(s)
Hasegawa Y, Kawachi S, Shimazu M, Hoshino K, Tanabe M, Fuchimoto Y, Obara H, Shinoda M, Shimizu H, Yamada Y, Akatsu T, Irie R, Sakamoto M, Morikawa Y, Kitajima S
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Journal Title
American Journal of Transplantation 7(9)
Pages: 2204-2207
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Discontinuation of living donor liver transplantation for PSC due to his tological abnormalities in intraoperative donor liver biopsy2007
Author(s)
Hasegawa, Y, Kawachi, S, Shimazu, M, Hoshino, K, Tanabe, M, Fuchimoto, Y, Obara, H, Shinoda, M, Shimizu, H, Yamada, Y, Akatsu, T, Irie, R, Sakamoto, M, Morikawa, Y, Kitajima, M
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Journal Title
American Journal of Transplantation 7(9)
Pages: 2204-2207
Description
「研究成果報告書概要(欧文)」より
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