E-cadherin promotes intraepithelial expansion of bladder carcinoma cells in an in vitro model of carcinoma in situ

High-grade transitional cell carcinomas (TCCs) of the urinary bladder are f requently associated with carcinoma irt situ, which may replace large areas of the mucosa of the urinary tract. The invasive component of TCCs often r eveals:a loss of expression of the cell-cell adhesion molecule E-cadherin, but the role of E-cadherin in the development and expansion of intraepithel ial neoplasia is unknown. To study the underlying mechanism of intraepithel ial expansion (IE), we have developed an IEE assay. Human TCC cell lines we re investigated in this IEE assay for their capacity to replace the surroun ding normal murine urothelial cells. In vitro IEE appeared to be prominent in three (SD, RT112, and 1207) of the four E-cadherin-positive cell lines. Although the two E-cadherin-negative cell lines (T24 and J82) were able to penetrate surrounding normal urothelium as single cells, they largely lacke d the capacity of IEE. These results prompted us to investigate whether the cell-cell adhesion molecule E-cadherin is an important determinant for IEE , T24 cells that were transfected with full-length mouse E-cadherin cDNA di splayed an enhanced IEE rate. Transfection did not influence their prolifer ative capacity their pattern and level of integrin expression, or their abi lity to expand in the absence of surrounding urothelium. The data suggest t hat E-cadherin-mediated cohesiveness is an important factor in the IEE of b ladder carcinoma cells. These observations argue for a dual, paradoxical ro le of E-cadherin in bladder tumorigenesis. On the one hand, E-cadherin prom otes the expansion of intraepithelial neoplasia; on the other hand, its los s correlates with invasive behavior.