Liver metastatic model for human gastric cancer established by orthotopic tumor cell implantation

We have established an orthotopic implantation model that is highly metasta tic to the liver. A human gastric carcinoma cell line, AZ521, with low capa city 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 f oci were subsequently implanted orthotopically, and me established a cell l ine, AZH5G, by repeating the in vivo stepwise selection method. This metast asizing line (AZH5G) developed liver metastasis in seven of eight (87.5%) c ases, whereas parental AZ521 developed in 3 of 20 (15.0%). The invitro grow th activities of AZH5G were lower than that of AZ521, although the in vivo tumorigenicity of AZH5G was clearly higher than that of AZ521. Motility ass ays demonstrated higher motility of AZH5G than of AZ521. Flow cytometric an alysis 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 AZH5C cells to laminin was lower than t hat of AZ521 cells. In contrast, the adhesive activity of AZH5G cells to fi bronectin was clearly higher than that of AZ521 cells. These findings sugge sted 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 mech anisms of liver metastasis and to develop a new therapeutic approach for hu man gastric cancer.