Bladder cancer cells acquire competent mechanisms to escape Fas-mediated apoptosis and immune surveillance in the course of malignant transformation

Mechanisms of resistance against Fas-mediated cell killing have been report ed in different malignancies. However, the biological response of immune es cape mechanisms might depend on malignant transformation of cancer cells. I n this study we investigated different mechanisms of immune escape in 2 wel l-differentiated low-grade (RT4 and RT112) and 2 poorly differentiated high -grade (T24 and TCCSUP) bladder cancer cell lines. Fas, the receptor of Fas -ligand, is expressed and shedded by human transitional bladder carcinoma c ell lines RT4, RT112, T24 and TCCSUP. Cytotoxicity and apoptosis assays dem onstrate that in spite of the Fas expression, poorly differentiated T24 and TCCSUP cells are insensitive towards either recombinant Fas-ligand or agon istic apoptosis-inducing monoclonal antibody against Fas. In poorly differe ntiated T24 and TCCSUP cell lines we were able to detect marked Fas-ligand protein by flow cytometry and Western blot analysis. In grade 1 RT4 and RT1 12 cells only minor expression of Fas-ligand possibly because of proteinase action. Fas-ligand mRNA translation or post-translational processing seems to be regulated differentially in the cancer cell lines depending on malig nant transformation. In co-culture experiments we show that poorly differen tiated cells can induce apoptosis and cell death in Jurkat cells and activa ted peripheral blood mononuclear cells. This in vitro study suggests that b ladder cancer cells can take advantage of different mechanisms of immune ev asion and become more competent in avoiding immune surveillance during tran sformation to higher-grade malignant disease. (C) 2001 Cancer Research Camp aign.