ABO blood-group antigens in oral cancer.
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.
Dabelsteen
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Department of Oral Diagnostics, School of Dentistry, University of Copenhagen, Nørre Alle 20, DK-2200 Copenhagen N, Denmark. ed@odont.ku.dk
Gao
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S
D000017:ABO Blood-Group System / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000097:blood*; D002465:Cell Movement; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D016695:Glycosyltransferases / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity; D009062:Mouth Neoplasms / Q000097:blood*; D011401:Promoter Regions, Genetic
D000017:ABO Blood-Group System; D016695:Glycosyltransferases