Glycodynamics of mucin biosynthesis in gastrointestinal tumor cells

Abstract

Glycoproteins found in the secretions and on the surfaces of cancer cells include mucins and mucin-like glycoproteins. These molecules have been shown to carry antigens that are characteristically expressed on cancer cells, including Tn and T antigens and Lewis epitopes. The structures of O-glycans are often abnormal in gastrointestinal tumors, or else are present in abnormal amounts, and these structures greatly contribute to the phenotype and biology of cancer cells. It has been shown that glycans of cancer cells have functional importance in cell adhesion, invasion and metastasis. The possible mechanisms leading to these cancer-specific changes in carbohydrate structures (termed glycodynamics) involve altered mRNA expression and catalytic activities of glycosyltransferases and sulfotransferases found in tissues and cells of gastrointestinal tumors. In a number of cases it has been possible to correlate enzyme changes with oligosaccharide structures. Different mechanisms have been suggested leading to the synthesis of cancer-specific Lewis, T and Tn antigens, but the regulation of cancer mucin antigens generally appears to be very complex and is poorly understood. The expression levels of specific mucin antigens and enzymes in gastro-intestinal tumors have diagnostic as well as prognostic value. These antigens also have potential for cancer immunotherapy. However, we first need to unravel the complexity of the control of glycosylation in cancer cells. Most importantly, studies of the functional implications of the glycodynamics in cancer cells, as related to cell adhesion and impact on the immune system will provide promising directions for future research.