Liver metastatic model for human gastric cancer established by orthotopic tumor cell implantation.
We have established an orthotopic implantation model that is highly metastatic to the liver. A human gastric carcinoma cell line, AZ521, with low capacity for liver metastasis was implanted as a single-cell suspension in the stomach of nude mice. The tumor cells derived from a few liver metastatic foci were subsequently implanted orthotopically, and we established a cell line, AZH5G, by repeating the in vivo stepwise selection method. This metastasizing line (AZH5G) developed liver metastasis in seven of eight (87.5%) cases, whereas parental AZ521 developed in 3 of 20 (15.0%). The in vitro growth activities of AZH5G were lower than that of AZ521, although the in vivo tumorigenicity of AZH5G was clearly higher than that of AZ521. Motility assays demonstrated higher motility of AZH5G than of AZ521. Flow cytometric analysis demonstrated that the expression of alpha 6-integrin significantly decreased in AZH5G (4.9% +/- 4.1%) compared to in AZ521 (17.7% +/- 8.1%) (p < 0.05). The adhesive activity of AZH5G cells to laminin was lower than that of AZ521 cells. In contrast, the adhesive activity of AZH5G cells to fibronectin was clearly higher than that of AZ521 cells. These findings suggested that changes in the expression of integrins on the cell surface might play an important role in metastatic ability. This well characterized line and its in vivo experimental model should be useful to investigate the mechanisms of liver metastasis and to develop a new therapeutic approach for human gastric cancer.
Yamaguchi
K
K
First Department of Surgery, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan. yamakoji@sapmed.ac.jp
Ura
H
H
Yasoshima
T
T
Shishido
T
T
Denno
R
R
Hirata
K
K
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D016228:Endothelial Growth Factors / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023421:Models, Animal; D009362:Neoplasm Metastasis / Q000503:physiopathology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016023:Integrins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2