Role of galectin-3 in adenocarcinoma liver metastasis

Abstract

Galectin-3 is a lactosamine-specific lectin that binds to laminin sugar-sites, and up-regulated expression of galectin-3 in primary colorectal cancer is involved in cancer progression and metastasis. Inhibitory effects of cell adhesion and liver metastasis of adenocarcinoma via portal vein by lectin-binding sugar and anti-galectin-3 antibody was examined to determine the role of galectin-laminin binding in cancer liver metastasis. Highly metastatic adenocarcinoma cell lines XK4-A3 and RPMI4788 were used in in vitro cell attachment and nude mice liver metastatic experiments, and inhibitory effects of anti-galectin-3 antibody or lectin-binding sugars were examined. The in vitro adhesion assay demonstrated that the anti-galectin-3 antibody and alpha-lactose inhibited XK4-A3 and RPMI4788 cell adhesion to laminin in a dose-dependent manner. The liver metastasis of XK4-A3 and RPMI4788 was reduced 50 and 60%, respectively (P<0.001) by alpha-lactose treatment. Anti-galectin-3 antibody also inhibited liver metastasis in a dose-dependent manner, and maximum inhibition rate was 66% for XK4-A3 and 90% for RPMI4788. Galectin-3 plays an important role in liver metastasis of adenocarcinoma by the mechanisms of galectin-3 binding to laminin. Inhibition of galectin-3 on cancer cell surface induces reduced cell attachment to laminin and liver metastasis.