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Towards defining roles and relationships for tenascin-C and TGF beta-1 in the normal and neoplastic urinary bladder

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JournalJournal of Pathology
DatePublished - Nov 2002
Issue number3
Volume198
Number of pages10
Pages (from-to)359-368
Original languageEnglish

Abstract

Tenascin-C (TN-C) is an extracellular matrix glycoprotein expressed along epithelial/stromal boundaries during tissue remodelling events, such as those that occur during morphogenesis, wound healing, and tumour invasion. Using clinical specimens and a range of in vitro models that simulate homeostasis, wound healing, and malignant progression, this study sought to establish the patterns of TN-C expression in normal and neoplastic bladder and to determine the role of exogenous transforming growth factor beta-1 (TGFbeta-1), interleukin-4 (IL-4), basic fibroblast growth factor (bFGF), tumour necrosis factor alpha (TNFalpha), and interferon gamma (IFNgamma) in the induction of TN-C expression by bladder uro-epithelial cells. The findings indicate that normal urothelial cells may express TN-C, with both TGFbeta-1 and IL-4 able to induce expression. TN-C was not expressed in neoplastic urothelium, although both TN-C and TGFbeta-1 may be involved in tissue remodelling during papillary tumour formation and invasion. Furthermore, the urothelium of high-grade papillary tumours and carcinoma in situ specimens exhibited little TGFbeta-1 immunoreactivity, compared with the urothelium of low-grade tumours and normal specimens, suggesting an association between TGFbeta-1 expression and urothelial differentiation. A tumour invasion model, in which established bladder cancer cell lines were seeded onto a normal bladder stroma, corroborated the evidence from the clinical specimens and demonstrated that TN-C was strongly expressed around foci of stromal invasion. Thus, TN-C immunoreactivity may provide an additional tool in the assessment of early stromal invasion in bladder cancer. Copyright (C) 2002 John Wiley Sons, Ltd.

    Research areas

  • bladder cancer, transitional cell carcinoma, tenascin, transforming growth factor beta 1, urothelium, TRANSITIONAL-CELL-CARCINOMA, GROWTH-FACTOR-BETA, EPITHELIAL-MESENCHYMAL INTERACTIONS, HUMAN UROTHELIAL CELLS, IN-VITRO, ENDOTHELIAL-CELLS, BASEMENT-MEMBRANE, TUMOR PROGRESSION, EXPRESSION, TISSUE

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