Ewing's sarcoma family tumors are sensitive to tumor necrosis factor-related apoptosis-inducing ligand and express death receptor 4 and death receptor 5.

摘要: In this study, we investigated the sensitivity of Ewing's sarcoma family tumors (ESFTs) children and adolescents to tumor necrosis factor-related apoptosis-inducing Ligand (TRAIL). TRAIL binds death receptors (DRs) DR4, DR5, DcR1, DcR2. Either DR4 or DR5 can induce apoptosis, whereas DcR1 DcR2 are considered inhibitory receptors. Nine 10 ESFT cell lines, including several that were Fas resistant, underwent apoptosis with through activation caspase-10, capase-8 (FLICE), caspase-3, caspase-9. contrast signaling pathway, but not caspase-8 Fas-associated domain-containing molecule, was recruited receptor-associated complex. We found 9 lines expressed both by Western blotting, TRAIL-resistant line only DR4. However, absent from surface in resistant two additional (three five tested lines), suggesting it may have been nonfunctional. On contrary, located on all four sensitive tested, being also DR5-negative blotting. agreement these findings, resistance overcome restoration levels transfection. Levels FLICE-inhibitory protein (FLIP) did correlate resistance, synthesis inhibition sensitize TRAIL. Because data suggested ESFTs mainly based presence DR4/DR5, 32 tissue sections immunohistochemistry. 23 tissues (72%) receptors, 8 (25%) one receptor only, 1 negative for both. Our finding wide expression DR4/DR5 vivo, combination their high vitro reported lack toxicity mice monkeys, suggests be a novel effective agent treatment ESFTs.