Sialic Acids and Cancer
- Pp. 381-403 (23)Alexandre S. Stephens, Christopher J. Day and Joe Tiralongo
Altered cell surface sialylation is a hallmark of cancer. Investigation of clinical samples, cell lines and animal models has revealed associations between aberrant sialylation and cancer progression. Total serum and lipid bound sialic acid (Sia) levels are elevated in many types of cancer displaying a positive correlation with cancer stage and grade. The expression of α2-3 and α2-6 linked Sia and the levels of sialylated structures sialyl-Tn, sialyl Lewis a (SLea) and sialyl Lewis x (SLex) are also elevated in cancer cases. The metastatic potential of cancer cells is positively correlated to the levels of terminal galactose and N-acetylgalactosamine sialylation and the activities and mRNA expression levels of sialyltransferases and sialidases/neuraminidases are also significantly altered in cancer. The potential mechanisms via which altered sialylation is contributed to the progression of cancer have been studied. Increased Sia expression on the surface of cancer cells can enhance cell-cell repulsion and such an effect can potentially promote the dispersion of cells from primary tumor encouraging metastasis. Enhanced invasion, migration and altered binding to extracellular matrix, which are cell characteristics associated with metastatic behaviour, have also been linked to changes in sialylation. Increased resistance to apoptosis which can confer a growth advantage and the elevated expression of selectin ligands, SLea and SLex, can facilitate the transport of cancer cells throughout the blood stream and participate in the docking of cancer cells to the vascular endothelium at distant sites have also been observed in cancer cells displaying aberrant sialylation.