Title | P-cadherin as a prognostic indicator and a modulator of migratory behaviour in bladder carcinoma cells. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Mandeville JA, Neto BSilva, Vanni AJ, Smith GL, Rieger-Christ KM, Zeheb R, Loda M, Libertino JA, Summerhayes IC |
Journal | BJU Int |
Volume | 102 |
Issue | 11 |
Pagination | 1707-14 |
Date Published | 2008 Dec |
ISSN | 1464-410X |
Keywords | Aged, Biomarkers, Tumor, Cadherins, Carcinoma, Transitional Cell, Cell Movement, Humans, Immunohistochemistry, Male, Neoplasm Invasiveness, Prognosis, Survival Analysis, Tissue Array Analysis, Transfection, Urinary Bladder Neoplasms |
Abstract | OBJECTIVE: To identify changes associated with P-cadherin expression in bladder cancer and evaluate the potential role of such events in determining the clinical outcome and cell behaviour, as the function of P-cadherin in normal epithelium is unknown, as is its potential role in neoplastic progression in different cancers. MATERIALS AND METHODS: In all, 536 bladder tumour specimens from 408 patients were assembled in seven tissue microarrays. Paraffin sections from each array were processed for immunohistochemistry to assess the expression of P-cadherin. The expression of P-cadherin was forced using lipofectin, followed by an assessment of migration and invasion potential using standard in vitro assays. RESULTS: The absence of P-cadherin staining was associated with muscle-invasive disease, grade 3 (P < 0.001) and nodal disease (P = 0.009). Similar results were obtained when considering cytoplasmic and unrestricted localization of P-cadherin (P < 0.001), except for nodal involvement. The group with cytoplasmic location of P-cadherin showed a shorter cancer-specific survival than the group with membrane location of P-cadherin (P = 0.03). Forced expression of P-cadherin in EJ and UM-UC-3 cells, that constitutively lack P-cadherin expression, resulted in modulation of catenin expression and enhanced migration of EJ and UM-UC-3/P-cadherin transfectants (>200%). CONCLUSIONS: These results showed that loss of expression, cytoplasmic relocation or unrestricted tissue location of P-cadherin was associated with a poor clinical outcome and prognosis in bladder cancer. From the in vitro work it is evident that P-cadherin plays a role in regulating the migration potential of bladder carcinoma cells. |
DOI | 10.1111/j.1464-410X.2008.08115.x |
Alternate Journal | BJU Int |
PubMed ID | 18990147 |
Related Faculty:
Massimo Loda, M.D.