Lewis (Le) antigens are fucosylated carbohydrates (oligosaccharides) linked to lipids or proteins and thus present as glycolipids or glycoproteins. As a well-known specialist in antibody fields, Creative Biolabs has paid attention to glycomics research for many years, including Lewis antigens, and has gained high recognition to be a top-ranking service supplier. With assistance by us to understand the pattern of the expression of Lewis antigens in normal tissues, together with the physiological functions, will set the framework to know their altered regulation and tumor-promoting abilities in the cancer context.
Fig.1 Different Lewis antigens. (Chandler, 2013)
Lewis antigens are G protein-coupled receptors and primarily synthesized by endodermal epithelia, but they’re observed in endodermal epithelia and red blood cells (RBCs) due to the transfer of glycolipids to RBCs. Lewis structures have been shown to be expressed in normal tissues on two major carbohydrate chains, type 1 and type 2, according to the linkage type between the Gal residue and the GlcNAc residue, β1,3 and β1,4, respectively. Type 1 chains contain Lewisa/b (Le-a/b), while type 2 chains contain Lewisx/y (Le-x/y).
Lewisa and Lewisb are two major antigens in the Lewis histo-blood group system. The Lewisb antigen is a product of two fucosyltransferases (FUTs), the a(1,3/1,4)fucosyltransferase (Lewis enzyme; Fuc-TIII; FUT3) encoded by the Lewis gene and an a(1,2)fucosyltransferase which is not necessary for the synthesis of Lewisa antigen. They are three common phenotypes including Le(a+b-), Le(a-b+), and Le(a-b-). Lewis antibodies are naturally occurring antibodies, almost the IgM type and exclusively present in Le(a-b-) individuals. Lewis antigens that are moderately expressed in healthy adult tissues have similar functions, however, in a different context. In epithelial tissues, Lewisx expression has been detected in the colon, stomach, salivary glands, kidneys, bladder, uterus, cervix, epididymis, and medulla, while Lewisy expression is mainly found in epithelial cells from the breast, lung, colon, stomach, pancreas, uterus, ovary, prostate, salivary glands, and Panneth cells of the small intestine.
Fig.2 Schematic diagram of type I histo-blood
group antigen synthesis in secretor
and non-secretor individuals. (Hu, 2018)
The Lewis locus encodes the FUTs responsible for synthesizing Lewis antigens. These transferases demonstrate similar expression to the secretor loci.
The Lewis transferase is a FUT3 which transfers fucose from GDP-Fuc to GlcNAc in type 1 or 2 chain. An α3 linkage is formed when transferred to a type 2 chain, and an α4 linkage is formed when attached to a type 1 chain because of prior occupancy of the Gal on the 4 or 3 position of GlcNAc, respectively. And the addition of fucose forms the Lewisa or Lewisx structure. Transfer of fucose to the terminal Gal in α1-2 to form the H antigen prior to the action of α3/4FucT is in charge of forming the Lewisb and Lewisy structure. Formation of the H antigen uses the same α1-2FucT for synthesizing the H precursor to A and B blood groups. In summary, Lewis antigens are generated by attachment of α3/4fucose to an unsubstituted type 1 or 2 chain to form Lewisa/x or to an H type 1 or 2 chain to form Lewisb/y antigens.
In terms of function, Lewisx is required for neutrophil transepithelial migration, and it exerts positive immunoregulation on dendritic cells through the engagement of C-type lectin receptor (CLR) dendritic cell-specific ICAM-3 grabbing non-integrin. Meanwhile, Lewisx is the predominant fucosylated antigen in the brain which facilitates cell-cell interactions involved in neuronal development. It is an epitope of stage-specific embryonic antigen-1 (SSEA-1) and currently used as a surface biomarker for the identification of neural stem cells.
Table.1 Clinical relevance of Lewis antigen overexpression in different types of cancers. (Blanas, 2018)
Aberrant glycosylation of cancer cells is recognized as a universal hallmark of tumorigenesis. Overexpression of fucosylated epitopes, such as type I (H1, Lewisa, Lewisb, and sialyl Lewisa) and type II (H2, Lewisx, Lewisy, and sialyl Lewisx) Lewis antigens, often occurs on the surface of cancer cells and are mainly attributed to upregulated expression of pertinent FUTs. However, the effects of fucose-containing moieties on cancer cells is not fully elucidated yet. If you want more information, please contact us by e-mails.
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