Towards Defining Roles and Relationships for tenascin-C and TGFbeta-1 in the Normal and Neoplastic Urinary Bladder

J Pathol. 2002 Nov;198(3):359-68. doi: 10.1002/path.1214.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma in Situ / metabolism
  • Carcinoma, Papillary / metabolism
  • Cytokines / pharmacology
  • Humans
  • Immunoenzyme Techniques
  • Mucous Membrane / drug effects
  • Mucous Membrane / metabolism
  • Neoplasm Proteins / metabolism
  • Neoplasm Seeding
  • Organ Culture Techniques
  • Organoids / metabolism
  • Tenascin / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Transforming Growth Factor beta1
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism*
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Biomarkers, Tumor
  • Cytokines
  • Neoplasm Proteins
  • TGFB1 protein, human
  • Tenascin
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1