DETECTION OF A POTENTIAL RECEPTOR FOR THE H-BLOOD-GROUP ANTIGEN ON RAT COLON-CARCINOMA CELLS AND NORMAL-TISSUES

Up-regulation of the synthesis of carbohydrate tumor-associated antige ns terminated by the disaccharide Fuc alpha 1-2Gal is frequent in colo n carcinoma and associated with poor prognosis, There is evidence that Fuc alpha 1-2Gal (H-disaccharide) structures increase cancer-cell mot ility and tumorigenicity by as-yet unknown mechanisms, Using polyacryl amide-based neoglycoconjugates, we looked for a potential receptor for this disaccharide, and observed that a neoglycoconjugate probe contai ning the H-disaccharide could bind rat colon-carcinoma cells in a dose -dependent manner, whereas very little binding was evidenced when a pr obe containing glucose was used, Binding of the H-disaccharide probe c ould be inhibited by the free H-disaccharide as well as by unlabeled n eoglycoconjugates containing a terminal H-disaccharide. The best inhib itor was the H-type-1 trisaccharide neoglycoconjugate, Histochemical d etection of the potential H-receptor was performed on rat normal tissu es and in situ 1,2-dimethylhydrazine-induced colon carcinomas, A stron g binding of the H-disaccharide probe was evidenced on most tumors tha t could be partly inhibited by the trisaccharide Fuc alpha 1-2Gal beta 1-4Glc and by the unlabeled H-disaccharide neoglycoconjugate, indicat ing carbohydrate specificity of the binding, Staining of normal coloni c mucosa was much weaker, Strong staining was also observed on some no rmal 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. (C) 1998 Wile y-Liss, Inc.