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

José Alexandre Ferreira, Paula A. Videira, Luís Lima, Sofia Pereira, Mariana Silva, Mylene Carrascal, Paulo F. Severino, Elisabete Fernandes, Andreia Almeida, Céu Costa, Rui Vitorino, Teresina Amaro, Maria J. Oliveira, Celso A. Reis, Fabio Dall'Olio, Francisco Amado, Lúcio Lara Santos

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Abstract

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.

Original languageEnglish
Pages (from-to)719-731
Number of pages13
JournalMolecular Oncology
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Bladder cancer
  • Glycosylation
  • Proliferative bladder cancer
  • Sialyl-Tn
  • ST6GalNAc.I
  • Tumour-associated glycans

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