Alterations of Membrane Glycopeptides in Human Colonic Adenocarcinoma

Abstract

Membrane glycopeptides were examined in human colonic adenocarcinoma and normal colonic mucosa. The carbohydrates of membrane glycopeptides were found to be markedly reduced in tumor tissue and the relative proportions of the various sugars were altered. Although all of the sugars were lower in tumor tissue when compared to the adjacent normal mucosa, galactosamine, fucose, and sialic acid were more significantly reduced. Examination of the blood group activity and lectin-binding properties of membrane glycopeptides revealed that specific carbohydrate structures had changed in the tumor tissue. Most striking of these changes was the disappearance of glycoprotein-associated blood group A activity. Assay of the enzyme responsible for synthesis of the blood group A determinant showed that this glycosyltransferase activity was greatly diminished in tumor tissue. A galactosyltransferase and a fucosyltransferase were also significantly lower in the tumor tissue whereas the levels of another galactosyltransferase and a sialyltransferase were unaltered. Glycosidase activities in the normal and tumor tissues were similar. The results show that an alteration in glycoprotein biosynthesis occurred during tumorigenesis that resulted in a modified membrane glycoprotein composition and that these changes are probably a reflection of reduced levels of the enzymes responsible for glycoprotein synthesis.Glycoproteins and glycolipids are ubiquitous in mammalian cells and are major components of cellular membranes (1-6). Glycopeptides isolated from the plasma membranes of cells such as erythrocytes and fibroblasts have diverse immunological properties, among them blood group and virus agglutinating activities (3,4). It has been shown that these properties are determined by the terminal sequence and linkage of sugars in glycoprotein and glycolipid structures. The surface membranes and the microsomal membranes of intestinal epithelial cells also contain various carbohydrate moieties (2,7,8).Phenomena characteristic of tumor growth such as alteration of cell-cell interactions and disturbance of normal immunological processes strongly implicate cellular membranes in the process of tumorous transformation. Differences in composition of membrane glycoproteins resulting from viral transformation of cells and in the metabolic systems which elaborate and degrade them have been reported (9-17). Although a consensus has not been reached, the studies uniAbbreviations: con A, concanavalin A; a1AGP-NANA, a,-acid glycoprotein minus sialic acid; OSM-NANA. ovine submaxillary mucin minus sialic acid; ac-AGP-NANA-GAL, a-acid glycoprotein minus sialic acid, minus galactose; NANA, N-acetylneuraminic acid.formly suggest that both quantitative and qualitative differences are induced in the membrane glycoproteins of cells after transformation. These changes apparently occur in both internally and externally located membranes (14,15). The majority of studies were performed on cultured cell systems in which the effects of various tumorigenic agents ...

Monoclonal antibodies to human colorectal epithelium: Markers for differentiation and tumour characterization

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“…In two well-differentiated cancers, the antigen was distributed in a pattern similar to that in normal colonic epithelial cells, with CEA located Vol. 49 predominantly along the luminal border of the malignant glands (Fig. 7A).…”

Reactivity of Gliadin and Lectins with Celiac Intestinal Mucosa1

“…The addition and rearrangement of glycoprotein carbohydrate side chains is regulated by different glycosyltransferase enzymes whose activity has been shown to be strictly related to the cell maturity and state of differentiation. It was thought that gluten-induced epithelial cell death and increased cell turnover is followed by incomplete cell maturation in the small intestine of patients with CD, thereby generating an augmentation of gluten binding sites and exacerbating the offensive effects of gliadin and probably lectins (24)(25)(26)(27).…”