Glycosylation in bladder cancer

Abstract

Complex carbohydrates are major components of the cell membrane and they play crucial roles in cell-cell and cell-extracellular matrix interactions, as well as in signal transduction. They consist of three kinds of molecular species; glycoproteins, proteoglycans, and glycosphingolipids. There is a distinct difference in carbohydrate profiles between normal and tumor tissues. The characteristic carbohydrate expression associated with malignant transformation is caused by "aberrant glycosylation" catalyzed by specific glycosyltransferases and glycosidases. A close relationship between blood type antigens and bladder cancer was first established in the 1960s, using the classic red-cell adherence test. Lectin immunohistochemical staining eventually replaced the red-cell adherence test. In the 1980s, several monoclonal antibodies were raised against complex carbohydrates, and the clinico-pathologic significance of blood type antigens in bladder cancer was investigated using these antibodies. Recent studies have demonstrated the high sensitivity and specificity of immunostaining for Lewis X antigen, a carbohydrate blood type antigen, in exfoliated cells from voided urine samples. Other than blood type antigens, the significance of aberrant glycosylation in bladder cancer has been demonstrated in a number of articles. For instance, overexpression of the ganglioside (an acidic glycosphingolipid which has sialic acid) GM3 induces apoptosis and reduces invasive potential in a bladder cancer cell line. Hyaluronic acid promotes tumor metastasis and is an accurate diagnostic marker for bladder cancer. The expression of N-acetylglucosaminyltransferase V and beta,1-6 branching N-linked oligosaccharides is closely related to low malignant potential in bladder cancer. Selectins and galectins, specific ligands for carbohydrate antigens, are also key molecules involved in the apoptosis and metastasis of cancer cells. Thus, proteoglycans, glycoproteins, and glycosphingolipids, and their ligands, play crucial roles in the malignant transformation, invasion, and metastasis of bladder cancer. A novel diagnostic and therapeutic approach may be possible by taking advantage of innovative techniques in glycobiology.