Up-regulation of the synthesis of
carbohydrate tumor-associated antigens terminated by the
disaccharide Fucalpha1-2Gal is frequent in colon
carcinoma and associated with poor prognosis. There is evidence that Fucalpha1-2Gal (H-
disaccharide) structures increase
cancer-cell motility and tumorigenicity by as-yet unknown mechanisms. Using
polyacrylamide-based neoglycoconjugates, we looked for a potential receptor for this
disaccharide, and observed that a neoglycoconjugate probe containing the H-
disaccharide could bind rat colon-
carcinoma cells in a dose-dependent manner, whereas very little binding was evidenced when a probe containing
glucose was used. Binding of the H-
disaccharide probe could be inhibited by the free H-
disaccharide as well as by unlabeled neoglycoconjugates containing a terminal H-
disaccharide. The best inhibitor was the H-type-1
trisaccharide neoglycoconjugate. Histochemical detection of the potential H-receptor was performed on rat normal tissues and in situ 1,2-dimethylhydrazine-induced colon
carcinomas. A strong binding of the H-
disaccharide probe was evidenced on most
tumors that could be partly inhibited by the
trisaccharide Fucalpha1-2Galbeta1-4Glc and by the unlabeled H-
disaccharide neoglycoconjugate, indicating
carbohydrate specificity of the binding. Staining of normal colonic mucosa was much weaker. Strong staining was also observed on some normal tissues, such as the spleen or lymph nodes, while others, such as lungs or liver, were negative. Probes containing
glucose or the Lewis-
a trisaccharide did not
stain tumors or normal tissues. These results provide preliminary evidence for the existence of H-specific binding sites, the number of which increases in colon
carcinoma.