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

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.

Descrição

This work was supported by Portuguese Foundation for Science and Technology (FCT) Postdoctoral grant SFRH/BPD/66288/2009 (Jose Alexandre Ferreira), PhD grant SFRH/BD/43399/2008 (Luis Lima), SFRH/BD/81860/2011 (Mariana Silva), SFRH/BD/45120/2008 (Paulo F. Severino) and by LPPC/Pfizer 2011 (Mylene Carrascal). This work was also financially supported by FCT (PTDC-SAU-ONC/112511/2009). FCT is co-financed by European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF).

Palavras-chave

Bladder cancer Glycosylation Proliferative bladder cancer Sialyl-Tn ST6GalNAc.I Tumour-associated glycans Molecular Medicine Genetics Cancer Research SDG 3 - Good Health and Well-being