Circulating AIM Prevents Hepatocellular Carcinoma through Complement Activation

被引:66
作者
Maehara, Natsumi [1 ]
Arai, Satoko [1 ]
Mori, Mayumi [1 ]
Iwamura, Yoshihiro [1 ]
Kurokawa, Jun [1 ]
Kai, Toshihiro [1 ]
Kusunoki, Shunsuke [1 ]
Taniguchi, Kaori [1 ]
Ikeda, Kazutaka [2 ]
Ohara, Osamu [3 ]
Yamamura, Ken-ichi [4 ]
Miyazaki, Toru [1 ,5 ,6 ]
机构
[1] Univ Tokyo, Fac Med, Ctr Dis Biol & Integrat Med, Lab Mol Biomed Pathogenesis, Tokyo 1130033, Japan
[2] Keio Univ, Inst Adv Biosci, Tsuruoka, Yamagata 9970052, Japan
[3] Kazusa DNA Res Inst, Dept Human Genome Res, Kisarazu, Chiba 2920818, Japan
[4] Kumamoto Univ, Ctr Anim Resources & Dev, Kumamoto 8600811, Japan
[5] Japan Sci & Technol Agcy, CREST, Tokyo 1130033, Japan
[6] Max Planck Univ Tokyo Ctr Integrat Inflammol, Tokyo 1130033, Japan
基金
日本学术振兴会;
关键词
FATTY LIVER-DISEASE; NONALCOHOLIC STEATOHEPATITIS; APOPTOSIS INHIBITOR; NATURAL-HISTORY; MACROPHAGE AIM; SP-ALPHA; EPIDEMIOLOGY; GLYCOPROTEIN; ENDOCYTOSIS; RESISTANCE;
D O I
10.1016/j.celrep.2014.08.058
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Hepatocellular carcinoma (HCC) is a widespread fatal disease and the third most common cause of cancer deaths. Here, we show the potent anti-HCC effect of the circulating protein AIM. As in adipocytes, AIM is incorporated into normal hepatocytes, where it interferes with lipid storage. In contrast, AIM accumulates on the HCC cell surface and activates the complement cascade via inactivating multiple regulators of complement activation. This response provokes necrotic cell death specifically in AIM-bound HCC cells. Accordingly, AIM(-/-) mice were highly susceptible to steatosis-associated HCC development, whereas no AIM(+/+) mouse developed the disease despite comparable liver inflammation and fibrosis in response to a long-term high-fat diet. Administration of AIM prevented tumor development in AIM(-/-) mice, and HCC induction by diethylnitrosamine was more prominent in AIM(-/-) than wild-type mice. These findings could be the basis for novel AIM-based therapeutic strategies for HCC.
引用
收藏
页码:61 / 74
页数:14
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