Targeting Selectins Mediated Biological Activities With Multivalent Probes

Selectins are type-I transmembrane glycoproteins that are ubiquitously expressed on activated platelets, endothelial cells, and leukocytes. They bind to cell surface glycoproteins and extracellular matrix ligands, regulate the rolling of leukocytes in the blood capillaries, and recruit them to inflammatory sites. Hence, they are potential markers for the early detection and inhibition of inflammatory diseases, thrombosis, cardiovascular disorders, and tumor metastasis. Fucosylated and sialylated glycans, such as sialyl Lewisx, its isoform sialyl Lewisa, and heparan sulfate, are primary selectin ligands. Functionalization of these selectin-binding ligands on multivalent probes, such as nanoparticles, liposomes, and polymers, not only inhibits selectin-mediated biological activity but is also involved in direct imaging of the inflammation site. This review briefly summarizes the selectin-mediated various diseases such as thrombosis, cancer and recent progress in the different types of multivalent probes used to target selectins.

Changes of the expression of Lewis blood group antigens in glycoproteins of renal cancer tissues.

Sialic acid and sialyl Lewisa/x are found on N- and O-glycans of many human malignant cells. Carbohydrate antigens can be used as tumor markers, and an increase of their levels in cancer cells is associated with tumor progression. The aim of this study was to assess the level of some Lewis blood group antigens on glycoproteins in tumor (cancer tissue), intermediate zone (adjacent to tumor tissue), and normal renal cortex/medulla (uninvolved by tumor). The study was performed on tissues taken from 30 patients. Relative amounts of sugar structures of proteins with molecular masses above 30 kDa were determined by ELISA-like test with biotinylated lectins: MAA (Maackia amurensis), SNA (Sambucus nigra), and monoclonal antibodies anti-sialyl Lewisa/x.∙ Higher expression of all examined structures was revealed in cancer tissues. Significant increases were observed for sialic acid linked α 2-3 in cancer tissues when compared to healthy ones and also among intermediate and healthy tissues. The sialic acid linked α 2-6 and sialyl Lewisx structures were significantly increased in cancerous cells when compared to normal and intermediate renal tissue. In case of sialyl Lewisa antigen, a significant difference was discovered between normal and intermediate tissue. Our results confirm that the examined Lewis antigens can be involved in tumor development. Their increase in cancer tissues can suggest their specific role in the process.