Defining the glycophenotype of squamous epithelia using plant and mammalian lectins. Differentiation‐dependent expression of α2,6‐ and α2,3‐linked N‐acetylneuraminic acid in squamous epithelia and carcinomas, and its differential effect on binding of the endogenous lectins galectins‐1 and ‐3

Abstract

A thorough characterization of the properties of squamous epithelial cells is necessary in order to improve our understanding of the functional aspects of normal development and malignant aberrations. Up to now, studies have focused almost exclusively on monitoring distinct protein markers. With our growing awareness of the coding function of glycan chains of cellular glycoconjugates and their interaction with receptors (lectins) in situ, defining the glycophenotype of these cells has become an important issue. Whereas the commonly applied plant lectins are tools used to map the presence and localization of biochemically defined saccharide epitopes, the introduction of endogenous (mammalian) lectins to this analysis enables us to take the step from monitoring the presence of glycan to understanding the functional implications by revealing ligand properties of the detected epitope for tissue lectin. Thus, in this study we investigated a distinct aspect of glycosylation using plant and mammalian lectins, i.e. the linkage type of sialylation. We first mapped the expression profile of the type of sialylation (alpha2,3- or alpha2,6-linked) by plant lectins. Based on the hypothesis that this factor regulates accessibility of ligands for endogenous lectins we introduced two labeled galectins to this study. Galectin-3 (but not galectin-1) binding was related to cell differentiation in normal adult and developing epithelia, cultured epidermal cells, and carcinomas derived from these epithelia. The presented data suggest that alpha2,6-linked N-acetyl-D-neuraminic acid moieties could serve to mask galectin-3-reactive glycoepitopes. As a consequence, monitoring of the linkage type of sialic acid in glycans by plant lectins therefore has implications for the extent of glycan reactivity with endogenous lectins, pointing to a potential function of changes in sialylation type beyond these cell and lectin systems.

Sialylation of 1 Integrins Blocks Cell Adhesion to Galectin-3 and Protects Cells against Galectin-3-induced Apoptosis

“…The idea that ␣2-6 sialylation serves as an "on-off switch" for galectin binding and function is supported by studies of both synthetic oligosaccharides (20,44) and cell surface glycans (21,22,30,(45)(46)(47). ST6Gal-I selectively modifies N-glycans on CD45 to negatively regulate gal-1-induced T cell death (21).…”

Galectin-3 Induces Death of Candida Species Expressing Specific β-1,2-Linked Mannans

“…Galectin-3 is expressed by epithelia lining the body surfaces that are exposed to Candida colonization, such as oral mucosa, corneal, and conjunctival epithelia, and intestinal epithelia (62)(63)(64)(65), that constitute the first line of host defense against Candida invasion. Although relatively high concentrations of soluble galectin-3 (20 M) were required to trigger Candida death in vitro, abundant galectin-3 has been detected in the local milieu surrounding inflammatory cells in human tissues (58), and galectin binding to extracellular matrix proteins has been shown to concentrate galectin (59).…”

Human Monocytes Recognize Porcine Endothelium via the Interaction of Galectin 3 and α-GAL

“…Holikova et al (35) have shown that removal of ␣(2, 6) and ␣(2, 3)sialic acid increases Galectin-3 binding. Porcine and humans differ in the structure of their sialic acid residues.…”