CD95 ligand-induced apoptosis of human medulloblastoma cells.
CD95 ligand (CD95L) is a cytotoxic cytokine that induces apoptosis in susceptible target cells. Medulloblastoma is the most common non-glial intrinsic malignancy of the brain. In this study, we have studied CD95-mediated apoptosis of human medulloblastoma cell lines. We found that DAOY, MED-1 and D-283 cells are susceptible to CD95L-induced apoptosis when RNA and protein synthesis are inhibited. Preexposure of D-283, but not DAOY or MED-1 cells, to interferon-gamma or tumor necrosis factor-alpha enhances CD95 expression and primes these cells for CD95-mediated apoptosis. Inhibitors of interleukin 1-converting enzyme (ICE)-like protease (caspase) activity block CD95L-induced cytotoxicity, suggesting that caspases mediate the death signal induced by CD95L in human medulloblastoma cells. Interestingly, medulloblastoma cells belong to an increasing number of tumor cell types that coexpress CD95 and CD95L. We conclude that CD95 may be a promising target of immunochemotherapy for human medulloblastoma.
Weller
M
M
Department of Neurology, University of Tübingen, Medical School, Germany. michael.weller@uni-tuebingen.de
Schuster
M
M
Pietsch
T
T
Schabet
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053222:Fas Ligand Protein; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008527:Medulloblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012334:RNA, Neoplasm; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D007371:Interferon-gamma