Gb3 Specific Neutra™ Antibody Products

Gb3 is initially produced as a preproprotein and subsequently cleaved into four distinct mature peptides. One of these peptides, resembles glicentin, an active enter glucagon. Two other peptides are secreted by gut endocrine cells and facilitate nutrient absorption through different mechanisms. The fourth peptide glucagon is a pancreatic hormone that counteracts insulin’s glucose-lowering effects by stimulating glycogenolysis and gluconeogenesis. Glucagon binds to a specific G-protein-coupled receptor, whose signaling pathway regulates cell proliferation.

Gb3 Signaling Pathway

Gb3 is a member of the (glyco)sphingolipid group, which contains structurally and functionally diverse molecules crucial for cell homeostasis. Besides modulating cell-cell interactions, they regulate proliferation, programmed cell death, and differentiation. The lipid moiety ceramide forms the scaffolding of all complex glycosphingolipids. Ceramide is synthesized de novo in the endoplasmic reticulum (ER), with a range of glycosyltransferases and glycosidases mediating its conversion into Gb3, as well as the catabolism of Gb3 back into ceramide. Specific enzymes regulate ceramide's further metabolism in the Golgi apparatus when it is transported from ER. Following synthesis, Gb3 translocates to the plasma membrane, where it either remains or is transported to lysosomes, and specific enzymes degrade it. The breakdown products are then reused for glycosphingolipid synthesis or other cellular metabolic processes.

Fig.1 Schematic illustration of the biosynthesis from ceramide to Gb3 and the catabolism of Gb3.^{1, 3}

Applications of Anti-Gb3 Antibodies

• The Immunochemistry Application of Anti-Gb3 Antibodies in Glycolipid Homeostasis

Silencing Vps11, a key component of both the class C core vacuole/endosome tethering complex and the homotypic fusion and protein sorting complex, promotes retrograde transport of Shiga toxin. This knockdown can mitigate the inhibitory effects resulting from the depletion of moesin and ezrin. Immunolabeling Gb3 with an anti-Gb3 antibody reveals that Gb3 levels decrease following moesin knockdown but are restored with concurrent knockdown of moesin and Vps11. Thus, Vps11 knockdown compensates for the reduced Gb3 levels caused by moesin depletion. Collectively, the anti-Gb3 antibody assists in underscoring the significance of Vps11 and further clarifying the mechanisms of glycolipid homeostasis.

• Anti-Gb3 MAb is a Targeted Approach for Inhibiting Tumor Angiogenesis and Progression

Inhibiting tumor vasculature growth is a key strategy in combating tumor progression. Plasma membrane glycosphingolipids remain relatively understudied among the diverse pro-angiogenic molecular targets. A notable therapeutic advantage has been observed with tumor immunotherapy targeting Gb3. Thus, a monoclonal antibody (mAb) targeting Gb3 has been thoroughly characterized and developed. Gb3 is overexpressed in proliferative endothelial cells compared to quiescent cells. The anti-Gb3 mAb impedes endothelial cell proliferation in vitro by decelerating cellular proliferation and extending the duration of mitosis. It effectively inhibits angiogenesis in aortic ring assays ex vivo and reduces NXS2 neuroblastoma development and liver metastases in A/J mice. Immunohistological analysis has revealed Gb3 expression exclusively in endothelial cells within metastases. Besides, treatment with anti-Gb3 mAb decreases tumor vessel density, confirming its specific action on tumor vasculature. These findings establish Gb3 as a promising target for angiogenesis inhibition and immunotherapy.

Fig.2 Immunolocalization of Gb3 in human microvascular endothelial cells using FITC-conjugated anti-Gb3 mAb.^{2, 3}

Creative Biolabs offers a selection of finely crafted antibodies targeting Gb3, developed using advanced recombinant techniques. Additionally, personalized customization services are provided to tailor neutralizing antibodies targeting Gb3 according to precise requirements.

REFERENCES

1. Feitz, Wouter JC, et al. "The Shiga toxin receptor globotriaosylceramide as therapeutic target in Shiga toxin E. coli mediated HUS." Microorganisms 9.10 (2021): 2157.
2. Desselle, Ariane, et al. "Anti-Gb3 monoclonal antibody inhibits angiogenesis and tumor development." PloS one 7.11 (2012): e45423.
3. Distributed Under open access license CC BY 4.0, without modification.