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...

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Veröffentlicht in:Journal of neuroimmunology 2005-05, Vol.162 (1), p.28-42
Hauptverfasser: Wischhusen, Jörg, Schneider, Dagmar, Mittelbronn, Michel, Meyermann, Richard, Engelmann, Hartmut, Jung, Gundram, Wiendl, Heinz, Weller, Michael
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container_end_page 42
container_issue 1
container_start_page 28
container_title Journal of neuroimmunology
container_volume 162
creator Wischhusen, Jörg
Schneider, Dagmar
Mittelbronn, Michel
Meyermann, Richard
Engelmann, Hartmut
Jung, Gundram
Wiendl, Heinz
Weller, Michael
description 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-α-induced apoptosis. Bispecific CD40xCD95 antibodies specifically kill glioma cells, disclosing the property of endogenous CD40 to facilitate death signalling.
doi_str_mv 10.1016/j.jneuroim.2005.01.005
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subjects Amino Acid Chloromethyl Ketones - pharmacology
Antibodies - pharmacology
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - physiology
Bispecific antibodies
Blotting, Northern - methods
Blotting, Western - methods
Caspases - metabolism
CD40
CD40 Antigens - immunology
CD40 Antigens - pharmacology
CD40 Antigens - physiology
CD40 Ligand - pharmacology
CD40 Ligand - physiology
Cell Line, Tumor
Cell Survival - drug effects
Cell Survival - physiology
Collagen Type XI - metabolism
Dose-Response Relationship, Drug
Drug Interactions
Fas Ligand Protein
fas Receptor - immunology
fas Receptor - metabolism
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Glioma
Glioma - metabolism
Glioma - pathology
Humans
Immunohistochemistry - methods
Immunoprecipitation - methods
Leupeptins - pharmacology
Membrane Glycoproteins - pharmacology
Neuroprotective Agents - pharmacology
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerases
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA Interference - physiology
RNA, Messenger - biosynthesis
Time Factors
TNF-R1 (p55)
Transfection - methods
Tumor Necrosis Factor-alpha - metabolism
Tumor Necrosis Factor-alpha - pharmacology
title Death receptor-mediated apoptosis in human malignant glioma cells: Modulation by the CD40/CD40L system
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