ESTABLISHMENT AND CHARACTERIZATION OF HUMAN GASTRIC-CARCINOMA LINES WITH HIGH METASTATIC POTENTIAL IN THE LIVER - CHANGES IN INTEGRIN EXPRESSION ASSOCIATED WITH THE ABILITY TO METASTASIZE IN THE LIVER OF NUDE-MICE

There is a need to establish animal models which are suitable for inve stigation of human gastric cancer metastasis to the liver. To this end , a human gastric carcinoma line, AZ521 was injected into the spleens of nude mice. Cells from the few liver metastatic foci of injected AZ5 21 were expanded in vitro and subsequently injected into the spleens o f nude mice. By repeating these procedures three times, we were able t o obtain a cell line, designated as AZ-H3c, with high metastatic poten tial in nude mice. Liver metastasis developed in 15 of 21 (71%) animal s injected with AZ-H3c, but in only 14% of those injected with parenta l AZ521. Further, AZ-H3c caused faster tumor development than did AZ52 1. However, the primary AZ-H3c tumors and liver metastatic AZ-H3c tumo rs showed essentially the same histological appearance. We also analyz ed the cell surface expression of adhesion molecules. The data showed that the expression of VLA-1, VLA-2, VLA-3, VLA-4, VLA-5 was enhanced in AZ-H3c. In contrast, the expression of VLA-6, alpha v beta 3, E-cad herin, ICAM-1 and LFA-1 was reduced in this high-metastatic line. Thes e results suggest that beta 1 integrins play an important role in the liver metastasis of human gastric carcinoma cells. Our high-metastatic line should be useful for studies aimed at the prevention of liver me tastasis.