E-selectin, also known as CD62E, that expressed mostly on endothelium, is a vascular adhesion molecule. Promoting leukocyte cell trafficking by the way of recognizing Proteins on ligand surfaces is its key role. It is barely expressed by resting endothelial cells. But it is expressed in the skin and bone marrow. Generally speaking, after inflammatory stimuli induce the expression of SELE, E-selectin is expressed. Consequently, de novo protein synthesis is required for E-selectin expression. E-selectin appears to take hours after stimulation and peaks up to hours after being exposed to an appropriate cytokine. E-selectin expression also is influenced by exposure to shear stress, the higher the shear stress, the more E-selectin.
When the interaction between Tumor cells and the endothelium and the tumor microenvironment is disrupted and affected, the dissemination and sensitization of the treatment of cancer cells can be achieved by blocking selectins. The mobilization of cancer cells is promoted by the selectins’ obstacle. This causes anoikis, which moreover increases their sensitivity and thus enhances the effect of chemotherapy. It manifests that selectin plays a key role. For instance, Since E-selectin was proven to refer to cancer cell trafficking, stem-like properties, and therapy resistance, it holds a new role. Further, It is proved that E-selectin is an important receptor in leukemia and myeloma. In addition, it is also crucial in solid tumors such as pancreatic, prostate, colon, and breast cancer cells. Moreover, when tumors that can metastasize to the bone marrow are present, E-selectin is raised. Many E-selectin ligands are expressed on migrating cancer cells including E-selectin ligand (ESL-1), L-selectin (CD62L), P-selectin glycoprotein ligand-1 (PSGL-1, CD162), homing cell adhesion molecule 1 (HCAM1; CD44), death receptor 3 (DR-3) and cutaneous lymphocyte-associated antigen (CLA).
Since anomalous Glycosylation patterns, the area of glycobiology in cancer has emerged. It is a potential target for Anticancer therapies that Sialic Acids and sialic acid-containing glycoconjugates associated with tumors become. The idea began with the research of sialyltransferase, an enzyme, that mostly operates to generate E-selectin ligands. E-selectin recognizes sialylated Carbohydrates/fucosylated Glycoprotein ligands, for example, ESL-1, PSGL-1, CD44 and CLA, and so on, they are all expressed on circulating leukocytes and overexpressed on cancer cells. It is proved that a similar system of cell trafficking is used for cancer cells, especially hematological malignancies, to leukocytes. By regulating homing and engraftment, E-selectin takes part in cancer cell trafficking and metastasis Inhibiting the interactions of E-selectin with its physiological glycoprotein ligand is a potential cure.
The structure has not been fully clarified. The sialylated fucosylated glycans, such as sialyl Lewis X (sLex), are proven to be important features of selectin ligands. Using the tetrasaccharide sLex as a lead start become drug development programs. The minimum epitope recognized by E-selectin is the tetrasaccharide sialyl Lewis X (sLex, Fig.1). The concentration of sLex to achieve 50% inhibition (IC50) was determined to be 1100µM in a static, cell-free E-selectin binding assay using immobilized E-selectin and a biotinylated sLea -polylysine conjugate as multivalent ligand. The simplified analogue 1 (Fig.1) is discovered which showed 30-fold improved potency (IC50 = 36 µM) compared with sLex through modifying sLex.
Fig.1 The structure of the tetrasaccharide sialyl Lewis X and the simplified analog 1. (Thoma, et al., 2001)
In consequence, E-selectin-specific inhibitors may have the potential to be used to eradicate cancer, due to their ability to be expressed in the tumor microenvironment. CD BioGlyco has accumulated rich experience in carbohydrate synthesis. Customers can contact our employees directly and we will respond promptly. If you are interested in our services, please contact us for more detailed information.
Reference
