DAG–1 Carcinoma Cell in Studying the Mechanisms of Progression and Therapeutic Resistance in Bladder Cancer

Objective:We describe a new human bladder carcinoma cell line (DAG–1) established from a resected bladder cancer fragment and maintained in culture for more than 5 years and over 300 passages. Methods and Results:Immunological, biochemical and molecular analysis showed that the DAG–1 cells (62 chromosomes) express the cytokeratines 8, 13, 18 and 20 that confirm their epithelial origin as well as numerous cytokine and cytokine receptor mRNAs. They secrete tissue–type plasminogen activator (t–PA), urokinase–type plasminogen activator (u–PA), plasminogen activator inhibitors (PAI–1 and PAI–2), and express u–PA receptors (u–PAR/CD87) at their surface. DAG–1 cells are resistant to TNFα– and IFNγ–induced apoptosis, two cytokines secreted in the urine of Calmette–Guérin bacillus–treated patients and involved in the tumor regression. Conclusion:The DAG–1 cell line is a useful tool, both in vitro and in vivo, to study the progression of bladder tumors and their mechanisms of resistance to immunotherapy in relation with PAI–2 and antioxidant enzymes.