Overexpression of tumour-associated carbohydrate antigen sialyl-Tn in advanced bladder tumours

•First comprehensive study on the expression pattern of carbohydrate antigen STn in bladder cancer.•STn is expressed by proliferative/invasive tumours with elevated risk of recurrence/progression.•STn is expressed in tumour-adjacent mucosa, underlining a field carcinogenesis effect.•Development of a bladder cancer cell model expressing STn, the MCRSTn+.•STn enhances motility and invasive capacity, showing its association with malignancy.

Little is known on the expression of the tumour-associated carbohydrate antigen sialyl-Tn (STn), in bladder cancer. We report here that 75% of the high-grade bladder tumours, presenting elevated proliferation rates and high risk of recurrence/progression expressed STn. However, it was mainly found in non-proliferative areas of the tumour, namely in cells invading the basal and muscle layers. STn was also found in tumour-adjacent mucosa, which suggests its dependence on a field effect of the tumour. Furthermore, it was not expressed by the normal urothelium, demonstrating the cancer-specific nature of this antigen. STn expression correlated with that of sialyltransferase ST6GalNAc.I, its major biosynthetic enzyme. The stable expression of ST6GalNAc.I in the bladder cancer cell line MCR induced STn expression and a concomitant increase of cell motility and invasive capability. Altogether, these results indicate for the first time a link between STn expression and malignancy in bladder cancer. Hence, therapies targeting STn may constitute new treatment approaches for these tumours.

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