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Vol.65 No.1,2,3 >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/2775

Title: 癌細胞はHMGB1を分泌し筋組織をエネルギー源として利用している
Other Titles: Cancer cells utilize the skeletal muscle as an energy resource using cancer-secreted HMGB1
Authors: 國安, 弘基
羅, 奕
米田, 純也
Keywords: HMGB1
plasma free amino acid profile
energy metabolism
Warburg effect
autophagy
Issue Date: 31-Jul-2014
Publisher: 奈良医学会
奈良県立医科大学
Citation: Journal of Nara Medical Association Vol.65 No.1,2,3 p.1-7
Abstract: Cancer cells are known to produce energy through aerobic glycolysis; however, the role of host tissues in cancer energy metabolism is unclear. Here, we aimed to elucidate the cancer-host energy production relationship, in particular, the association between cancer energy production and host muscle. High mobility group box(HMGB)-l increased during the development and progression of colorectal cancer(CRC), which decreased pyruvate kinase(PK) M1 expression and PK activity in the muscle through the receptor for advanced glycation end products. However, muscle mitochondrial energy production was maintained. In contrast, HMGB1 increased lactate fermentation in CRC cells. In the muscle, HMGB1 treatment induced autophagy by decreasing phosphorylated mTOR levels and increasing autophagy-associated proteins. Autophagy increased plasma glutamate levels and 13^C-glutamine integration into acetyl-CoA in the muscle. In a dimethylhydrazine-induced mouse colon carcinogenesis model, the plasma free amino acid profile was altered, and glutamine increased, which was associated with a temporal HMGB1 increase in serum and colonic mucosa, a decrease in PKM1, and autophagy induction. These differences disappeared when HMGB1 was neutralized with an antibody. In a mouse subcutaneous CRC tumor model, PKMl expression decreased and 13^C-glutamine was integrated into acety1-CoA in the muscle. In 13^C-glutamine muscle-integrated mice with implanted CRC tumors, 13^C-glutamine integration was detected in acety1-CoA in the muscle and in lactate in the cancer cells. However, integration in the tumor was decreased by HMGB1 neutralization, glutamine targeting by DON, and glutaminase knockdown. These findings suggest that HMGB1 usurps the muscle to supply glutamine to cancer cells as an energy source.
URI: http://hdl.handle.net/10564/2775
ISSN: 13450069
Appears in Collections:Vol.65 No.1,2,3

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