首页|A novel animal model for in vivo study of liver cancer metastasis

A novel animal model for in vivo study of liver cancer metastasis

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AIM:To establish an animal model with human hepatocyte-repopulated liver for the study of liver cancer metastasis.METHODS:Cell transplantation into mouse livers was conducted using alpha-fetoprotein (AFP)-producing human gastric cancer cells (h-GCCs) and h-hepatocytes as donor cells in a transgenic mouse line expressing urokinase-type plasminogen activator (uPA) driven by the albumin enhancer/promoter crossed with a severe combined immunodeficient (SCID) mouse line (uPA/SCID mice).Host mice were divided into two groups (A and B).Group A mice were transplanted with h-GCCs alone,and group B mice were transplanted with h-GCCs and h-hepatocytes together.The replacement index (RI),which is the ratio of transplanted h-GCCs and h-hepatocytes that occupy the examined area of a histological section,was estimated by measuring h-AFP and h-albumin concentrations in sera,respectively,as well as by immunohistochemical analyses of h-AFP and human cytokeratin 18 in histological sections.RESULTS:The h-GCCs successfully engrafted,repopulated,and colonized the livers of mice in group A (RI =22.0％ ± 2.6％).These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures,which is a characteristics feature of gastric cancers.The serum h-AFP level reached 211.0 ± 142.2 g/mL (range,7.1-324.2 g/mL).In group B mice,the h-GCCs and h-hepatocytes independently engrafted,repopulated the host liver,and developed colonies (RI =12.0％ ± 6.8％ and 66.0％ ± 12.3％,respectively).h-GCC colonies also showed typical adenocarcinomatous glandular structures around the h-hepatocyte-colonies.These mice survived for the full 56day-study and did not exhibit any metastasis of h-GCCs in the extrahepatic regions during the observational period.The mice with an h-hepatocyte-repopulated liver possessed metastasized h-GCCs and therefore could be a useful humanized liver animal model for studying liver cancer metastasis in vivo.CONCLUSION:A novel animal model of human liver cancer metastasis was established using the uPA/SCID mouse line.This model could be useful for in vivo testing of anti-cancer drugs and for studying the mechanisms of human liver cancer metastasis.

Urokinase-type plasminogen activator/severe combined immunodeficient mouseMouse with humanized liverLiver cancer metastasisAlpha-fetoprotein-producing gastric cancer cells

Shinsuke Fujiwara、Hikaru Fujioka、Chise Tateno、Ken Taniguchi、Masahiro Ito、Hiroshi Ohishi、Rie Utoh、Hiromi Ishibashi、Takashi Kanematsu、Katsutoshi Yoshizato

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Clinical Research Center, National Hospital Organization Nagasaki Medical Center and Division of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 856-8652, Japan

Liver Research Laboratory, PhoenixBio Co., Ltd, Hiroshima 739-8511,Japan

Yoshizato Project, CLUSTER, Hiroshima Prefectural Institute of Industrial Science and Technology, Hiroshima 739-8511, Japan

Division of Surgery Ⅱ, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 856-8652, Japan

Liver Research Center, Osaka City University, Graduate School of Medicine, Osaka 532-0025, Japan

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2012

10.3748/wjg.v18.i29.3875

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(29)
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