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Metabolomic profiling of the liver bearing human colon cancer metastasis in superimmunodeficient NOG mice
Author(s) -
Ohmura Mitsuyo,
Handa Kan,
Nishime Chiyoko,
Mizushima Tomoko,
Kawai Kenji,
Hishiki Takako,
Yamamoto Takehiro,
Wakui Masatoshi,
Suemizu Hiroshi,
Nakamura Masato,
Suematsu Makoto
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1000.10
Subject(s) - gluconeogenesis , hypoglycemia , metastasis , glycogen , metabolome , metabolomics , colorectal cancer , glycolysis , cancer research , endocrinology , medicine , cancer , biology , pathology , metabolism , bioinformatics , insulin
Hypoglycemia is one of the important events in paraneoplastic syndrome caused by solid tumors. Although metabolic feature of solid tumors characterized by Warburg effect has been thought to account for an important factor causing hypoglycemia, roles of responses of the host against tumor development remain largely unknown. In order to examine mechanisms by which tumor development causes hypoglycemia, we have performed biochemical assessment using established liver metastasis model with superimmunodeficient NOD/scid/γ null (NOG) mice transplanted with the mutant GFP expressing human‐derived colon cancer cells. The results of PCNA immunoreactivities, systemic hypoglycemia, decreased glycogen storage in the liver and impairment of alanine‐induced gluconeogenesis, as well as data from metabolome and flux analysis using hepatic parenchymal cells with mass‐labeled compounds such as 13 C‐glucose, led us to suggest that, during cancer metastasis, regenerative responses of parenchymal cells requiring DNA synthesis promote large demand for utilization of carbohydrates and amino acid‐derived nitrogen, serving as an alternative mechanism causing hypoglycemia besides increased consumption of glucose in tumor cells by themselves.