Sialic Acid as a Target for the Development of Novel Antiangiogenic Strategies

Abstract

Sialic acid is associated with glycoproteins and gangliosides of eukaryotic cells. It regulates various molecular interactions, being implicated in inflammation and cancer, where its expression is regulated by sialyltransferases and sialidases. Angiogenesis, the formation of new capillaries, takes place during inflammation and cancer, and represents the outcome of several interactions occurring at the endothelial surface among angiogenic growth factors, inhibitors, receptors, gangliosides and cell-adhesion molecules. Here, we elaborate on the evidences that many structures involved in angiogenesis are sialylated and that their interactions depend on sialic acid with implications in angiogenesis itself, inflammation and cancer. We also discuss the possibility to exploit sialic acid as a target for the development of novel antiangiogenic drugs.

Biological Functions and Analytical Strategies of Sialic Acids in Tumor

“…Tumor cells grow in a hypoxia environment where sialic acids play an important role in tumor angiogenesis. Sialylation status could affect the growth factor-receptor interactions and related signal transduction in angiogenesis [77]. Gangliosides, one type of sialyl-glycosphingolipid, can be incorporated into the membrane of endothelial cells, increasing cell responsiveness to AGFs [78,79].…”

Coronaviruses: Is Sialic Acid a Gate to the Eye of Cytokine Storm? From the Entry to the Effects

“…The biological and physical properties of sialoglycans, including the negative charge and high hydrophilicity of cell membranes, regulate cell-cell and cell-extracellular matrix interactions [ 17 , 18 , 19 , 20 ]. Due to sialic acid glycotopes ubiquity it is biologically important in biological recognition and immune responses [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. According to Läubli and Varki sialoglycans expressed in the mammalian glycocalyx can be considered as self-associated molecular patterns (SAMPs) that can interact with the individual immune receptors presented on the same cell membranes and orchestrate inflammatory reactions within damaged tissues [ 29 ].…”

The Paired Siglecs in Brain Tumours Therapy: The Immunomodulatory Effect of Dexamethasone and Temozolomide in Human Glioma In Vitro Model

“…The cell membrane sialic acids play critical role as a regulators of adhesion-related cell-cell interaction underlying immune recognition [12,13]. The aberrantly sialylated tumour-specific glycotopes reduce cancer immunogenicity by the hiding of cell surface antigens, however, the tumour immune evasion is mainly facilitated by immune receptor families, such as the most of CD33-related sialic acid-binding immunoglobulin like lectins (Siglecs), that recognize cancer sialoglycans and transmit suppressive signals [14,15]. In the brain, the binding of polysialic acid (PSA) with microglial Siglec-11 receptor seem to be closely associated with the restriction of the immune function initiated by immunoreceptor tyrosine-based inhibitory motif (ITIM)-coupled signalling pathway [16,17].…”