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

被引:29
作者
Wischhusen, J
Schneider, D
Mittelbronn, M
Meyermann, R
Engelmann, H
Jung, G
Wiendl, H
Weller, M
机构
[1] Univ Tubingen, Sch Med, Hertie Inst Clin Brain Res, Dept Gen Neurol, D-72076 Tubingen, Germany
[2] Univ Tubingen, Sch Med, Inst Brain Res, D-72076 Tubingen, Germany
[3] Univ Munich, Inst Immunol, D-80336 Munich, Germany
[4] Univ Tubingen, Sch Med, Inst Cell Biol, Dept Immunol, D-72076 Tubingen, Germany
关键词
glioma; CD40; apoptosis; TNF-R1 (p55); bispecific antibodies;
D O I
10.1016/j.jneuroim.2005.01.005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2005 Elsevier B.V All rights reserved.
引用
收藏
页码:28 / 42
页数:15
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