LIVER METASTASIS AND ADHESION TO THE SINUSOIDAL ENDOTHELIUM BY HUMAN COLON-CANCER CELLS IS RELATED TO MUCIN CARBOHYDRATE CHAIN-LENGTH

Mucin production by human colon cancer cells correlates with liver met astasis in animal models, but it: is not known which steps in metastas is depend on specific alterations in mucin synthesis. Clonal variants of cell line LS174T selected for differences in mucin core carbohydrat e expression have been further characterized biochemically, and tested for their ability to participate in metastasis-related events. LS-C m ucin contains truncated carbohydrates enriched for sialyl Tn and these cells bind to basement membrane matrix to a greater extent: than LS-B cells. This binding is partially inhibit-able by antibody to sialyl T n. LS-B produces more fully glycosylated mucin and preferentially bind s to hepatic sinusoidal endothelial cells and E-selectin through sialy lated peripheral mucin-associated carbohydrate structures. Adhesion of LS-B to endothelial cells is inhibited by neutralizing antibody to E- selectin, and inhibition of glycosylation or desialylation of LS-B muc in abrogates binding to E-select-in in vitro. LS-B cells spontaneously metastasized from cecum to liver and colonized the liver of athymic m ice after splenic-portal injection to a significantly greater extent t han LS-C, suggesting that expression of peripheral mucin carbohydrate structures is most important for metastasis of human colon cancer cell s. (C) 1998 Wiley-Liss, Inc.