Establishment of two new human bladder carcinoma cell lines, CAL 29 and CAL 185. Comparative study of cell scattering and epithelial to mesenchyme transition induced by growth factors

We describe here two new human urothelial carcinoma cell lines, CAL 29 and CAL 185, established from two patients with high-grade tumours and which di splay very different properties in vitro. We have shown that CAL 29 cells w ere tumorigenic in mice and expressed characteristic features of both cell scattering and transition from epithelial to mesenchymal phenotype (EMT) af ter triggering by the EGF receptor ligands, TGF-alpha and EGF. At the oppos ite, the CAL 185 cells were not tumorigenic in mice and neither scattered n or expressed vimentin intermediary filaments in the presence of growth fact ors. We further demonstrated that CAL 29 cell scattering was reversible aft er growth factor removal and that both scattering and EMT were markedly imp aired after treatment with MEK, Src and P13-kinase inhibitors suggesting th at these kinases might be important components of the cellular responses to EGF and TGF-alpha leading to scattering and EMT These agents could help to understand the intracellular pathways involved in invasiveness and to find new targets for limiting metastasis. In conclusion, these two new cell lin es could be good models to dissect the molecular mechanisms involved in inv asion and metastasis development in human bladder cancer. (C) 2001 Cancer R esearch Campaign.