Lewis Blood Group Antigens in Salivary Glands and Stratified Epithelium: Lack of Regulation of Lewis Antigen Expression in Ductal and Buccal Mucosal Lining Epithelia

Mandel, Ulla; Ørntoft, Torben F.; Holmes, Eric H.; Sørensen, Henning Osholm; Clausen, Henrik; Hakomori, Sen‐itiroh; Dabelsteen, Erik

doi:10.1159/000461356

Cited by 6 publications

(6 citation statements)

References 6 publications

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“…The antibodies with references to their specificity are shown in Table II. Tissue antigens were detected using double-layer immunohistochemical staining techniques, as described previously in detail (Mandel et al, 1991). Primary antibodies were applied overnight at 4°C and fluoroscein isothiocyanateor alkaline phosphatase-conjugated rabbit antibodies against mouse, rat, or human immunoglobulins (DAKO, Copenhagen, Denmark), as appropriate, were used as the second layer.…”

Section: Methodsmentioning

confidence: 99%

Altered Expression of Epithelial Cell Surface Glycoconjugates and Intermediate Filaments at the Margins of Mucosal Wounds

Dabelsteen

Grøn²,

Mandel³

et al. 1998

Journal of Investigative Dermatology

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Alterations in cell to cell adhesion are necessary to enable the type of cell movements that are associated with epithelial wound healing and malignant invasion. Several studies of transformed cells have related epithelial cell movement to changes in the cell surface expression of the carbohydrate structures represented by the ABO blood group antigens and, in particular, by Lewis antigens and their biosynthetic precursors. To study further the relationship between cell surface carbohydrates and keratinocyte cell movement, experimental wounds were created in human oral mucosa and examined by immunohistochemical methods for their expression of selected cytokeratins (K5, K16, K19), basement membrane components (laminin alpha5 and gamma2-chains, BP180, collagen IV and collagen VII), and blood group antigen precursor structures Le(x), sialosyl-Le(x), Le(y), H antigen, N-acetyllactosamine, and sialosyl-T antigen. The changes induced by wounding in the expression of collagen IV, laminin gamma2-chain (laminin-5), and laminin alpha5-chain were similar to those found in skin wounds and served to define the region of epithelial movement. This region was found to show a marked increase in staining for both Lewis antigen Y (Le(y)) and H blood group antigen, and decreased staining of Le(x), thus indicating an upregulation in wounded epithelium of the fucosyltransferases responsible for the synthesis of the H antigen. The changes in carbohydrate expression extended beyond the wound margin into the nonwounded epithelium, a pattern of expression similar to K16, which was also strongly upregulated in both the outgrowth and the adjacent nonwounded epithelium. These findings provide further support for an influence of such carbohydrate structures on the migratory behavior of epithelial cells.

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Section: Methodsmentioning

confidence: 99%

Altered Expression of Epithelial Cell Surface Glycoconjugates and Intermediate Filaments at the Margins of Mucosal Wounds

Dabelsteen

Grøn²,

Mandel³

et al. 1998

Journal of Investigative Dermatology

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“…Half of the population is blood group O, and 20% of the A/B individuals do not express A/B due to their nonsecretor status. In the O phenotype, the A/B precursor is transformed into the difucosylated structures Le b and Le y , whereas in the non-secretors, the monofucosylated structures Le a and Le x are found (Mandel et al, 1991). It is known that specific strains of pathogens bind to carbohydrates of the histo-blood-group family, and that individuals devoid of carbohydrates are less likely to be infected (Stapleton et al, 1992).…”

Section: Function Of the Abo Antigenmentioning

confidence: 99%

ABO Blood-group Antigens in Oral Cancer

Dabelsteen

Gao

2005

J Dent Res

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Tumor progression is often associated with altered glycosylation of the cell-surface proteins and lipids. The peripheral part of these cell-surface glycoconjugates often carries carbohydrate structures related to the ABO and Lewis blood-group antigens. The expression of histo-blood-group antigens in normal human tissues is dependent on the type of differentiation of the epithelium. In most human carcinomas, including oral carcinoma, a significant event is decreased expression of histo-blood-group antigens A and B. The mechanisms of aberrant expression of blood-group antigens are not clear in all cases. A relative down-regulation of the glycosyltransferase that is involved in the biosynthesis of A and B antigens is seen in oral carcinomas in association with tumor development. The events leading to loss of A transferase activity are related, in some instances, to loss of heterozygosity (LOH) involving chromosome 9q34, which is the locus for the ABO gene, and in other cases, to a hypermethylation of the ABO gene promoter. The fact that hypermethylation targets the ABO locus, but not surrounding genes, suggests that the hypermethylation is a specific tumor-related event. However, since not all situations with lack of expression of A/B antigens can be explained by LOH or hypermethylation, other regulatory factors outside the ABO promoter may be functional in transcriptional regulation of the ABO gene. Altered blood group antigens in malignant oral tissues may indicate increased cell migration. This hypothesis is supported by studies showing that normal migrating oral epithelial cells like malignant cells show lack of expression of A/B antigens, and by studies that target ABH antigens to key receptors controlling adhesion and motility, such as integrins, cadherins, and CD-44.

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“…accumulating over the years to suggest that the Lewis and secretor systems at the phenotypic level in some populations, particular Polynesians [7], are more complex than first thought. Further complexities are seen with the differential expression of Lewis antigens in different tissues [8,9] and a-4-fucosyltransferase activity in epithelial tissues of red-cell Lewis-negative individuals [lo]. It now appears that the biosynthesis of Lewis antigens is much more complex than the interaction of allelic coding and noncoding genes at the Lewis (Le) and secretor (Se) loci.…”

Section: Introductionmentioning

confidence: 99%

Detection and Characterization of Lewis Antigens in Plasma of Lewis‐Negative Individuals Evidence of Chain Extension as a Result of Reduced Fucosyltransferase Competition

1994

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Nonacid plasma glycolipids from Lewis-negative individuals of nonsecretor, partial-secretor and secretor phenotypes were prepared and separated by thin-layer chromatography and immunostained with radiolabelled Lewis antibodies. Lewis-positive plasma and intestinal epithelial cell glycolipids from Caucasians representing the four recognized Lewis and secretor combined phenotypes were used as controls. By presenting these purified total glycolipids in a cell-free environment to Lewis antibodies we were able to demonstrate the presence of small amounts of Lewis antigens in Lewis-negative individuals. It is shown that lactotetraosylceramide and extended precursor glycolipids are present in all Le(a-b-) nonsecretors. Le(a) was detected in 1 of the 3 Le(a-b-) nonsecretor plasmas and in the intestinal sample of the same phenotype. Lactotetraosylceramide was absent but H type 1 and Le(b) were both present in all group O Le(a-b-) secretors, and extended H type 1 reactive structures were also found in the partial secretor. These results clearly demonstrate that although the Lewis-negative phenotype exists at the serological level, this phenotype is not an 'all-or-nothing' phenomenon at the chemical level. We also show that in the presence of reduced fucosyltransferase activity, increased elongation of the precursor chain occurs, which allows us to postulate that fucosylation of the precursor prevents or at least markedly reduces chain elongation.

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Lewis Blood Group Antigens in Salivary Glands and Stratified Epithelium: Lack of Regulation of Lewis Antigen Expression in Ductal and Buccal Mucosal Lining Epithelia

Cited by 6 publications

References 6 publications

Altered Expression of Epithelial Cell Surface Glycoconjugates and Intermediate Filaments at the Margins of Mucosal Wounds

Altered Expression of Epithelial Cell Surface Glycoconjugates and Intermediate Filaments at the Margins of Mucosal Wounds

ABO Blood-group Antigens in Oral Cancer

Detection and Characterization of Lewis Antigens in Plasma of Lewis‐Negative Individuals Evidence of Chain Extension as a Result of Reduced Fucosyltransferase Competition

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