Death receptor-mediated apoptosis in human malignant glioma cells: modulation by the CD40/CD40L system.
CD40, a TNF-R-related cell surface receptor, is shown here to be expressed by glioma cells in vitro and in vivo. Glioma cell lines expressing low levels of CD40 at the cell surface resist cytotoxic effects of CD40L. CD40 gene transfer sensitizes glioma cells to CD40L. Inhibition of protein synthesis potentiates cell death which involves CD40 clustering and caspases 8 and 3 processing. CD40-transfected LN-18 cells acquire resistance to CD95L. In contrast, subtoxic concentrations of CD40L strongly sensitize these cells for TNF-alpha-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.
Wischhusen
Jörg
J
Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Medical School, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
Schneider
Dagmar
D
Mittelbronn
Michel
M
Meyermann
Richard
R
Engelmann
Hartmut
H
Jung
Gundram
G
Wiendl
Heinz
H
Weller
Michael
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D019013:CD40 Antigens / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D023201:CD40 Ligand / Q000494:pharmacology / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D024161:Collagen Type XI / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D007976:Leupeptins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D000906:Antibodies; D000970:Antineoplastic Agents; D019013:CD40 Antigens; C499319:COL11A2 protein, human; D024161:Collagen Type XI; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007976:Leupeptins; D008562:Membrane Glycoproteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; D023201:CD40 Ligand; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde