ENHANCED SIALYLATION OF MUCIN-ASSOCIATED CARBOHYDRATE STRUCTURES IN HUMAN COLON-CANCER METASTASIS

Background & Aims: Patients with mucinous colon cancers often have a p oor prognosis. The aim of this study was to determine whether metastat ic potential depends on specific alterations in mucin-associated carbo hydrate structures, Methods: A quantitative scoring system was used to examine the expression of mucin-associated carbohydrates in paired hu man primary colon cancers and metastases and in cecal tumors and liver metastases from an animal model of metastasis. Adhesion of metastatic cells to basement membrane and endothelial ligands was examined. Resu lts: Metastases expressed a decrease in mucin core structures Tn and T , a reciprocal increase in sialyl T and sialyl Tn, and an increase in peripheral sialyl Le(x) compared with the primary tumors from which th ey arose, Altered expression of sialylated mucin structures resulted f rom selective metastasis of cells that produce sialomucins. Antibodies to sialylated epitopes or desialylation inhibited adhesion of metasta tic cells to basement membranes. Neutralizing antibody to endothelial- associated E-selectin (a ligand for sialyl Le(x)) inhibited adhesion o f metastatic cells to cytokine-activated hepatic endothelial cells, an d inhibition of sialomucin with antisense to the MUC2 gene inhibited a dhesion to E-selectin. Conclusions: Increased sialylation of mucin-ass ociated carbohydrates is characteristic of colon cancer cells that are most likely to metastasize. Sialylated carbohydrate structures on muc in play a role in adhesive interactions involving both basement membra ne and endothelial-associated ligands.