HOMOTYPIC ADHESION THROUGH CARCINOEMBRYONIC ANTIGEN PLAYS A ROLE IN HEPATIC METASTASIS DEVELOPMENT

We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of li ver-metastatic cells in SCID mice. This cell line strongly expressed C EA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homot ypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and su bjected to an in vitro adhesion and aggregation assay. Further, to stu dy the role of CEA in the hepatic metastasis of cells with high metast atic potential, LSLM4 cells were treated with anti-CEA antibody, and t he inhibition of hepatic metastasis after splenic injection in vivo wa s examined, There was a 62% decrease in the homotypic adhesion of anti -CEA antibody-treated (100 mu g/ml) LS-LM4 cells under a Ca2+-free con dition as compared with the control (P<0.01). Anti-CEA antibody (100 m u g/ml) inhibited cell aggregation under a Ca2+-free condition (P<0.05 ). Treatment with anti-E-cadherin antibody (60 mu g/ml) plus anti-CEA antibody (100 mu g/ml) inhibited cell aggregation more potently than a nti-E-cadherin antibody treatment alone in the presence of Ca2+. In vi vo, there was a 75% decrease in the number of hepatic metastatic nodul es in the G125 anti-CEA antibody-treated group as compared with the co ntrol group (P<0.01). Similarly, there was a 40% decrease in the diame ter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated gro up as compared with the control (P<0.01), These results suggest that i ncreased metastatic potential to the liver is at least partly due to i ncreased homotypic binding mediated by CEA.