O-linked mucin-type glycoproteins in normal and malignant colon mucosa: lack of T-antigen expression and accumulation of Tn and sialosyl-Tn antigens in carcinomas.
The expression of carbohydrate core-structures on O-linked glycoproteins was examined in fetal (n = 6), infantile (n = 2), normal adult (n = 15), and malignant (n = 22) colorectal tissue by means of monoclonal antibodies (MAbs) specific for Tn (GalNAc alpha 1-O-R), sialosyl-Tn (NeuAc alpha 2-6GalNAc alpha 1-O-R), and T (Gal beta 1-3GalNAc alpha 1-O-R) antigens. Immunolabelling of solubilized malignant tissue, separated by SDS-PAGE, showed expression of Tn and sialosyl-Tn antigens on 3 molecules of similar mw (230, 210, and 170 kDa), whereas no T antigens could be detected. Immunohistochemical techniques showed that fetal colon mucosa expressed Tn antigens but no sialosyl-Tn antigens. Infantile colon mucosa, however, expressed Tn as well as sialosyl-Tn antigens, and normal adult colon mucosa cells expressed no Tn antigens but sialosyl-Tn in 2 out of 6 biopsies from cecum, which indicates occurrence post partum of alpha-6-NeuAc-transferase. Endothelium in normal adult mucosa showed expression of both Tn and sialosyl-Tn antigens; 82% of carcinoma tissue sections expressed Tn antigens, and 73% expressed sialosyl-Tn antigens in mucin or cytoplasm, or on luminal cell membranes. T antigens could be detected neither in normal mucosa cells at any stage of development, nor in carcinomas. The possibility exists that this could be due to masking of T antigen. Mucin-type blood-group A antigens which contain an internal T-disaccharide were demonstrated in 4 out of 4 A1 tumors by means of MAb HH5. However, urea-containing SDS-PAGE analysis demonstrated an HH5 binding to molecules different from those binding anti-Tn. In remote morphologically normal and abnormal crypts in colons from carcinoma patients, both Tn and sialosyl-Tn antigens were expressed in secreted mucin in 40% of the cases. The data indicate an expression of O-linked Tn and sialosyl-Tn core structures in fetal and infantile colon and in colorectal carcinomas.
Orntoft
T F
TF
Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
Harving
N
N
Langkilde
N C
NC
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis*; D015295:Antigens, Tumor-Associated, Carbohydrate; D000957:Antigens, Viral, Tumor / Q000032:analysis*; D003106:Colon / Q000276:immunology; D015179:Colorectal Neoplasms / Q000032:analysis / Q000276:immunology*; D005333:Fetus; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D000957:Antigens, Viral, Tumor; C057387:mucinous carcinoma-associated antigen; C055491:sialosyl-Tn antigen