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Human astrocytic brain tumors express AP02L/TRAIL
J Rieger1, H Ohgaki, P Kleihues
1Department of Molecular Neurology, University of Tübingen, Germany.
Acta Neuropathologica
|February 4, 1999
Summary
Tumor necrosis factor family cytokine APO2 ligand (APO2L) is expressed in human glioma cells and brain tumors. This suggests APO2L may regulate apoptosis in glial neoplasms, independent of the CD95/CD95L system.
Area of Science:
- Oncology
- Molecular Biology
- Neuroscience
Background:
- APO2 ligand (APO2L) is a tumor necrosis factor (TNF) superfamily cytokine.
- APO2L interacts with agonistic (DR4, DR5) and antagonistic (DcR1, DcR2) receptors.
- Malignant glioma cells express agonistic receptors and are sensitive to APO2L-induced apoptosis.
Purpose of the Study:
- To investigate the expression of APO2L in human glioma cell lines and primary astrocytic brain tumors.
- To determine if APO2L plays a role in apoptosis regulation in glial neoplasms.
Main Methods:
- Analysis of APO2L mRNA and protein expression in 8 human glioma cell lines in vitro.
- Immunohistochemistry using a monoclonal antibody to APO2L on 23 primary astrocytic brain tumors (including low-grade astrocytomas and glioblastomas).
- Assessment of APO2L immunoreactivity in non-neoplastic brain tissues (glia, neurons, reactive astrocytes).
Main Results:
- All 8 cultured human glioma cell lines expressed APO2L mRNA and protein.
- APO2L immunoreactivity was detected in all 23 primary astrocytic brain tumors analyzed.
- Non-neoplastic glia and neurons lacked APO2L immunoreactivity, with the exception of reactive astrocytes.
Conclusions:
- APO2L is expressed in human glioma cell lines and astrocytic brain tumors in vivo.
- APO2L expression is largely restricted to neoplastic glial cells, distinguishing them from normal glia and neurons.
- A second death ligand/death receptor system involving APO2L may regulate apoptosis in human glial neoplasms, in addition to the CD95/CD95L system.