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 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.
Galanina
O
O
Shemyakin Institute of Bio-organic Chemistry, Russian Academy of Sciences, Moscow.
Hallouin
F
F
Goupille
C
C
Bovin
N
N
Le Pendu
J
J
D000017:ABO Blood-Group System / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D004187:Disaccharides / Q000378:metabolism*; D005260:Female; D006001:Glycoconjugates / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000017:ABO Blood-Group System; D004187:Disaccharides; D006001:Glycoconjugates; D037102:Lectins