Death receptor-mediated apoptosis in human malignant glioma cells: Modulation by the CD40/CD40L system

Article ID	Journal	Published Year	Pages	File Type
9194648	Journal of Neuroimmunology	2005	15 Pages	PDF

Abstract

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-Î±-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.

Keywords

CD40L ECL FCS IFN-γ CD40 DISC FADD CHX PARP MG-132 FLIP BHK IAP TRAF TRADD SFI DR4/5 Death receptor 4/5 CD95L zVAD-fmk FLICE inhibitory protein TNF TNF receptor-associated death domain DEVD-AMC hsp70 PBS DMEM mAb PBMC FITC PHA TBS HRP Phytohemagglutinin Dulbecco's modified Eagle's medium Monoclonal antibody Bispecific antibodies interferon-γ interleukin enhanced chemiluminescence baby hamster kidney Tris-buffered saline Apoptosis standard error of the mean fetal calf serum peripheral blood mononuclear cells cycloheximide TNF receptor-associated factor Fab tumor necrosis factor fluorescein isothiocyanate TRAIL antigen-binding fragment CD40 ligand CD95 ligand TNF-related apoptosis-inducing ligand Phosphate-buffered saline SEM inhibitor of apoptosis polymerase chain reaction PCR Horseradish peroxidase heat-shock protein 70 Fas-associated protein with death domain poly (ADP-ribose) polymerase death-inducing signaling complex Glioma