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 hu-man 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 56 day-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. 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 hu-man 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 analyzes of h-AFP and human cytokeratin 18 in histological sections .RESULTS: The h-GCCs s These mice had moderately differentiated adenocarcinomatous lesions with disrupted glandular structures, which is a characteristics feature of gastric cancers. The serum h-AFP (RI = 22.0% ± 2.6%). 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 were 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 56 day-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 meta stasis 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.