Towards defining roles and relationships for tenascin-C and TGFbeta-1 in the normal and neoplastic urinary bladder.
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.
Booth
Catherine
C
Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York YO10 5YW, UK.
Harnden
Patricia
P
Selby
Peter J
PJ
Southgate
Jennifer
J
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009366:Neoplasm Seeding; D009924:Organ Culture Techniques; D009940:Organoids / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016207:Cytokines; D009363:Neoplasm Proteins; C508960:TGFB1 protein, human; D019063:Tenascin; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1