Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells.

The extracellular functions of galectin-7 (p53-induced gene 1) are largely unknown. On the surface of neuroblastoma cells (SK-N-MC), the increased GM1 density, a result of upregulated ganglioside sialidase activity, is a key factor for the switch from proliferation to differentiation. We show by solid-phase and cell assays that the sugar chain of this ganglioside is a ligand for galectin-7. In serum-supplemented proliferation assays, galectin-7 reduced neuroblastoma cell growth without the appearance of features characteristic for classical apoptosis. The presence of galectin-3 blocked this effect, which mechanistically resembles that of galectin-1. By virtue of carbohydrate binding, galectin-7 thus exerts neuroblastoma growth control similar to galectin-1 despite their structural differences. In addition to p53-linked proapoptotic activity intracellularly, galectin-7, acting as a lectin on the cell surface, appears to be capable of reducing cancer cell proliferation in susceptible systems.

Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting.

BACKGROUND: Knowledge of the expression of the galectins in human colon carcinomas is mainly restricted to galectin-3 and, to a lesser extent, galectin-1. The current study analyzed the prognostic values contributed by galectin-1, galectin-3, galectin-4, and galectin-8 in cases of colon carcinoma. METHODS: The authors selected 55 colon carcinomas (including 10 Dukes A, 16 Dukes B, 15 Dukes C, and 14 metastatic tumors that the authors labeled "Stage D"). The immunohistochemical levels of expression of the four galectins were determined quantitatively by means of computer-assisted microscopy. RESULTS: The data from the current study indicate that the four galectins under study are associated with significant and separate prognostic values that depend on the Dukes stage of the colon tumor. In particular, the authors observed a significant prognostic value associated with galectins-1, -3, and -4 in Dukes A and B colon tumors. In addition, significant prognostic value also was associated with galectin-8 in Dukes C and D colon tumors. The prognostic values associated with the levels of expression of galectin-1 and galectin-4 in Dukes A and B tumors appear to be independent of the Dukes stage. The same feature was observed when galectin-4 and galectin-8 were analyzed in the complete series. CONCLUSIONS: The data from the current study strongly suggest that galectins-1, -3, and -4 may be involved in the early stages of human colon carcinoma development and that galectin-8 is involved in the later stages.

Fine specificity of domain-I of recombinant tandem-repeat-type galectin-4 from rat gastrointestinal tract (G4-N).

Galectins, a family of beta-galactoside-specific endogenous lectins, are involved in regulating diverse activities such as proliferation/apoptosis, cell-cell (matrix) interaction and cell migration. It is presently unclear to what extent the carbohydrate fine specificities of the combining sites of mammalian galectins overlap. To address this issue, we performed an analysis of the carbohydrate-recognition domain (CRD-I) near the N-terminus of recombinant rat galectin-4 (G4-N) by the biotin/avidin-mediated microtitre plate lectin-binding assay with natural glycoproteins (gps)/polysaccharide and by the inhibition of galectin-glycan interactions with a panel of glycosubstances. Among the 35 glycans tested for lectin binding, G4-N reacted best with human blood group ABH precursor gps, and asialo porcine salivary gps, which contain high densities of the blood group Ii determinants Galbeta1-3GalNAc (the mucin-type sugar sequence on the human erythrocyte membrane) and/or GalNAcalpha1-Ser/Thr ( Tn ), whereas this lectin domain reacted weakly or not at all with most sialylated gps. Among the oligosaccharides tested by the inhibition assay, Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc was the best. It was 666.7 and 33.3 times more potent than Gal and Galbeta1-3GlcNAc, respectively. G4-N has a preference for the beta-anomer of Gal at the non-reducing ends of oligosaccharides with a Galbeta1-3 linkage, over Galbeta1-4 and Galbeta1-6. The fraction of Tn glycopeptide from asialo ovine submandibular glycoprotein was 8.3 times more active than Galbeta1-3GlcNAc. The overall carbohydrate specificity of G4-N can be defined as Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc (lacto- N -tetraose)>Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc (lacto- N -neo-tetraose) and Tn clusters>Galbeta1-4Glc and GalNAcbeta1-3Gal>Galbeta1-3GalNAc>Galbeta1-3GlcNAc>Galbeta1-4GlcNAc>GalNAc>Gal. The definition of this binding profile provides the basis to detect differential binding properties relative to the other galectins with ensuing implications for functional analysis.

Defining the glycophenotype of squamous epithelia using plant and mammalian lectins. Differentiation-dependent expression of alpha2,6- and alpha2,3-linked N-acetylneuraminic acid in squamous epithelia and carcinomas, and its differential effect on binding of the endogenous lectins galectins-1 and -3.

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.