Lewis X (Lex) and sialyl Lewis X (sLex) are carbohydrate blood group antigens important in cell adhesion. On cell membranes, Lex and sLex may be expressed on glycoproteins or glycosphingolipids (GSLs). The latter are complex macromolecules consisting of an oligosaccharide moiety covalently linked to a ceramide lipid tail. Similar to glycoproteins, Lex and sLex glycans expressed on GSLs can be either simple or multifucosylated, complex, branched, long-chain oligosaccharides. Developmental changes in Lex and sLex GSL expression may play a role in embryonic development and organogenesis. On neutrophils and platelets, sLex GSLs may function as the physiologic ligand for endothelial E-selectin, mediating rolling of platelets and neutrophils along activated endothelium. Likewise, endothelial sLex GSLs may function as ligands for Lselectin on lymphocytes. In lens, the age-dependent increase in Lex GSL expression may contribute to cataractogenesis via Lex-Lex homotypic adhesion, leading to spatial rearrangement of lens fibers and lens opacification. In malignancy, neoexpression of Lex and sLex GSLs by many tumors may contribute to tumor metastasis via increased adherence to vascular endothelium and platelets. In hematopoietic cells, biosynthesis of Lex and sLex GSLs reflects the action of multiple glycosyltransferases. Lewisx and sLex GSLs may also be chemically synthesized where they have been very useful in structure-function studies of selectin recognition and binding.
The nature of mucins expressed and secreted from colon cancer tumors is discussed. Two mucin-type molecules, MUC1 and the leukocyte marker CD43 (leukosialin), have been found in a model tumor cell line (COLO 205) as well as in clinical colon cancer cells. The sialyl-Lewis a expressing MUC1 and CD43 mucins can inhibit leukocyte adhesion to E-selectin endothelial cells and also NK cell mediated killing of target cells. The results propose that mucins secreted from tumor cells could interfere with the immune systems possibilities of eliminating tumor cells. The expression of CD43 in colon adenoma and cancer cells could be involved in the tumor progression.
Sucrase-isomaltase is a type II transmembrane glycoprotein that is expressed at the brush-border of epithelial cells in the small intestine where it is important for the degradation of sucrose and some of the products of starch digestion. The unique expression pattern of SI together with its specific structural features makes the protein ideally suited as a model for several cell-biological processes. This will be illustrate in this review by the following topics: i) the special structural features of SI ii) the specific expression pattern of this protein and its regulation iii) the role of apical transport mechanisms in the transport of SI to the apical membrane iv) the mechanisms responsible for the transport failures that cause congenital SI deficiencies v) the role of SI in the signal transduction cascade that takes place upon binding of a bacterial toxin to SI.