Biochemical, pathological and oncological relevance of Gb3Cer receptor

Abstract

Glycosphingolipids are amphipathic molecules composed of hydrophilic oligosaccharide chain and a hydrophobic ceramide part, located primarily in the membrane microdomains of animal cells. Their oligosaccharide chains make them excellent candidates for the cell surface recognition molecules. Natural glycosphingolipid, globotriaosylceramide (Gal α1-4, Gal β1-4, Glc β1-1, ceramide), is also called CD77 and its expression was previously associated with proliferating centroblasts undergoing somatic hypermutation, but it has been demonstrate that globotriaosylceramide is not a reliable marker to discriminate human centroblasts from centrocytes. Globotriaosylceramide constitutes rare P k blood group antigen on erythrocytes, and it is also known as Burkitt's lymphoma antigen. On endothelial cells, globotriaosylceramide plays as the receptor for bacterial toxins of the Shiga family, also called verotoxins. Precise biological function and significance of globotriaosylceramide expression on endothelial cells remains to be the subject of many studies and it is believed globotriaosylceramide represents an example of a glycolipid antigen able to transduce a signal leading to apoptosis. In past decade, cancer researches put a great afford in determining new therapeutic agents such as bacterial toxins against tumor malignancies. Reports have demonstrated that verotoxin-1 induces apoptosis in solid tumor cell lines expressing globotriaosylceramide such as astrocytoma, renal cell carcinoma, colon cancer and breast cancer due to verotoxin-1 high specificity and apoptosis-inducing properties, and therefore, it is suggested to be an anticancer agent. Verotoxins have been investigated weather they could reduce treatment side-effects and toxicity to normal tissues and become a new oncological tool in cancer labeling.

Structure-dependent Pseudoreceptor Intracellular Traffic of Adamantyl Globotriaosyl Ceramide Mimics

“…Third, Gb 3 and verotoxin internalization and intracellular traffic provide a probe of the molecular basis of retrograde transport to the ER (58). Fourth, Gb 3 is up-regulated in many human tumor cells, and thus verotoxin itself (59, 60, 61) or the B subunit pentamer coupled to cytotoxic drugs (62,63) offers new antineoplastic approaches (64). In this area also, as with HUS, endothelial cells within the neovasculature express Gb 3 and are VTsensitive (65,66).…”

Identification of a Novel Streptococcal Adhesin P (SadP) Protein Recognizing Galactosyl-α1–4-galactose-containing Glycoconjugates

“…It has been shown that the carbohydrate-binding pentameric B-subunit of E. coli verotoxin causes apoptosis in susceptible endothelial cells, such as the Eahy.926 hybridoma cell line, upon binding to the GbO3 glycolipid receptor (64,65), which makes the interaction of GbO3 with endogenous and exogenous ligands a potential target for therapies. The availability of the SadP with its distinct and well characterized Gal␣1-4Gal binding specificity could be a useful tool in studies aiming at these goals.…”

Streptococcal Adhesin P (SadP) contributes to Streptococcus suis adhesion to the human intestinal epithelium

“…Gb3/CD77 receptors are abundant in various host tissues including human and pig small intestine in the precursor (Gb3/CD77) or mature form (globotetraosylceramide Gb4) [13, 14]. Furthermore, Gb3/CD77 is a receptor for adhesin-mediated binding to host tissues of multiple human pathogens and serves as receptor for bacterial toxins (Shiga toxins, Stx) [15]. …”