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Towards defining roles and relationships for tenascin‐C and TGFβ‐1 in the normal and neoplastic urinary bladder
Author(s) -
Booth Catherine,
Harnden Patricia,
Selby Peter J,
Southgate Jennifer
Publication year - 2002
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1214
Subject(s) - urothelium , stromal cell , biology , tenascin , tenascin c , pathology , extracellular matrix , epithelium , transforming growth factor , urinary bladder , bladder cancer , cancer research , cancer , medicine , endocrinology , urinary system , microbiology and biotechnology , genetics , fibronectin
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 β‐1 (TGFβ‐1), interleukin‐4 (IL‐4), basic fibroblast growth factor (bFGF), tumour necrosis factor alpha (TNFα), and interferon gamma (IFNγ) 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 TGFβ‐1 and IL‐4 able to induce expression. TN‐C was not expressed in neoplastic urothelium, although both TN‐C and TGFβ‐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 TGFβ‐1 immunoreactivity, compared with the urothelium of low‐grade tumours and normal specimens, suggesting an association between TGFβ‐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 © 2002 John Wiley & Sons, Ltd.