Influence of the microenvironment on invasiveness of human bladder carcinoma cell lines

To investigate the importance of the microenvironment in bladder cancer inv asion, a panel of six bladder carcinoma cell lines (SD, RT112, JON, 1207, T 24, and J82) was tested in both in vitro and in vivo invasion assays. Furth ermore, invasiveness was correlated with the expression of components of th e E-cadherin-catenin complex. The E-cadherin-negative cell lines, T24 and J 82, displayed a high in vitro invasive capacity, whereas the E-cadherin-pos itive cell lines, SD and JON, completely lacked in vitro invasive capacity. In contrast, in vivo invasion was noted for all cell lines, with the excep tion of cell line JON. Most notably, SD formed highly invasive tumors in vi vo. The in vivo invasiveness of the E-cadherin-positive bladder carcinoma c ell lines was associated with a heterogeneous expression of the E-cadherin- catenin complex. The discrepancy between in vitro and in vivo invasive beha vior implies that, in vivo, the microenvironment plays an important role in the establishment of the invasive phenotype. In addition, it was found tha t orthotopic xenografting of 1207 and T24 bladder carcinoma cells resulted in site-specific tumor take and an enhanced tumor outgrowth and invasivenes s, respectively, compared with heterotopic (i.e., subcutaneous) inoculation . We conclude that the site-specific growth and invasion of the bladder car cinoma cell lines in vivo and the observed assay specific invasion (in vitr o vs in vivo) points to an effect of the local (bladder) microenvironment o n tumor cell behavior.