Loss of caspase-8 expression in neuroblastoma is related to malignancy andresistance to TRAIL-induced apoptosis

Background and Procedures, NB-derived cell lines were tested for their sens itivity to apoptosis induced by the tumor-selective apoptotic ligand TRAIL. Noninvasive S-type cell lines are highly sensitive to TRAIL, whereas invas ive N-type cell lines are resistant. Results. Although both S- and N-type c ell lines express TRAIL-R2, FADD, and caspases-3 and -10, only S-type cells express caspase-8. Reduced levers of caspase-8 protein were also observed in a stage IV NE tumor when compared to a ganglioneuroma. The caspase-8 gen e is not deleted in either N-type NE cell lines or high-stage tumors, and e xpression can be induced by demethylation. Conclusions. Therefore, caspase- 8 expression is silenced in malignant NE, which correlates to tumor severit y and resistance to TRAIL-induced apoptosis. (C) 2000 Wiley-Liss, Inc.