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

Jörg Wischhusen, Dagmar Schneider, Michel Mittelbronn, Richard Meyermann, Hartmut Engelmann, Gundram Jung, Heinz Wiendl, Michael Weller*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

31 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)28-42
Number of pages15
JournalJournal of Neuroimmunology
Volume162
Issue number1-2
DOIs
Publication statusPublished - May 2005
Externally publishedYes

Keywords

  • Apoptosis
  • Bispecific antibodies
  • CD40
  • Glioma
  • TNF-R1 (p55)

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