Enhanced sialylation of mucin-associated carbohydrate structures in human colon cancer metastasis

Abstract

Backgrounds & aims: Patients with mucinous colon cancers often have a poor prognosis. The aim of this study was to determine whether metastatic potential depends on specific alterations in mucin-associated carbohydrate structures.

Methods: A quantitative scoring system was used to examine the expression of mucin-associated carbohydrates in paired human 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.

Results: 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 they arose. Altered expression of sialylated mucin structures resulted from selective metastasis of cells that produce sialomucins. Antibodies to sialylated epitopes or desialylation inhibited adhesion of metastatic cells to basement membranes. Neutralizing antibody to endothelial-associated E-selectin (a ligand for sialyl Le(x)) inhibited adhesion of metastatic cells to cytokine-activated hepatic endothelial cells, and inhibition of sialomucin with antisense to the MUC2 gene inhibited adhesion to E-selectin.

Conclusions: Increased sialylation of mucin-associated carbohydrates is characteristic of colon cancer cells that are most likely to metastasize. Sialylated carbohydrate structures on mucin play a role in adhesive interactions involving both basement membrane and endothelial-associated ligands.