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Review
, 6 (1)

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis X in Gastrointestinal Cancers

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Review

Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis X in Gastrointestinal Cancers

Marco Trinchera et al. Biology (Basel).

Abstract

The tetrasaccharide structures Siaα2,3Galβ1,3(Fucα1,4)GlcNAc and Siaα2,3Galβ1,4(Fucα1,3)GlcNAc constitute the epitopes of the carbohydrate antigens sialyl-Lewis a (sLea) and sialyl-Lewis x (sLex), respectively, and are the minimal requirement for selectin binding to their counter-receptors. Interaction of sLex expressed on the cell surface of leucocytes with E-selectin on endothelial cells allows their arrest and promotes their extravasation. Similarly, the rolling of cancer cells ectopically expressing the selectin ligands on endothelial cells is potentially a crucial step favoring the metastatic process. In this review, we focus on the biosynthetic steps giving rise to selectin ligand expression in cell lines and native tissues of gastrointestinal origin, trying to understand whether and how they are deregulated in cancer. We also discuss the use of such molecules in the diagnosis of gastrointestinal cancers, particularly in light of recent data questioning the ability of colon cancers to express sLea and the possible use of circulating sLex in the early detection of pancreatic cancer. Finally, we reviewed the data dealing with the mechanisms that link selectin ligand expression in gastrointestinal cells to cancer malignancy. This promising research field seems to require additional data on native patient tissues to reach more definitive conclusions.

Keywords: cancer diagnosis; cancer malignancy; carbohydrate antigens; glycosylation.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure and biosynthesis of Lewis antigens. Monosaccharides are depicted. Blue square: N-acetylglucosamine (GlcNAc); yellow square: N-acetylgalactosamine (GalNAc); yellow circle: galactose (Gal); red triangle: fucose (Fuc); pink diamond: sialic acid (Sia). Anomers, linkage positions, and enzymes involved in the reactions are indicated. All enzymes known to be able to perform a reaction are listed, note that only some of them are proven to be expressed in gastrointestinal tissues, as detailed in the text.
Figure 2
Figure 2
Proposed model of the elevation of circulating CA19.9 in pancreatic cancer patients. The inversion of polarity occurring in malignant ductal cells [125] together with the obstruction of the cancerous ducts determine reabsorption by the blood of the molecules normally secreted by the organ [121,124]. According to recent data [40], the expression of type 1 chain Lewis antigens in the pancreas is regulated by the individual glycosyltransferase pattern, which is not deregulated in cancer. Consequently, serum CA19.9 levels increase only in those patients actually expressing the antigen in their normal ducts. Non-malignant pancreatic diseases causing obstruction, such as chronic pancreatitis, are expected to determine partially overlapping elevation of circulating antigens. Sugars are depicted as in Figure 1.

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