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Soluble TNF-alpha receptors are constitutively shed and downregulate adhesion molecule expression in malignant
T C Chen1, D R Hinton, B D Sippy
1Department of Neurosurgery, University of Southern California School of Medicine, USA.
Abstract:
The regulation of adhesion molecule expression in malignant gliomas by tumor necrosis factor-alpha (TNF) and soluble TNF receptors (TNFR) was examined in the malignant glioma cell line A-172 and in 2 primary glioblastoma cell cultures (LA-492 and LA-567). A-172 cells expressed only the p55 TNF receptor transcripts and protein. The 2 primary cell cultures expressed both the p55 and p75 TNF receptors. In A-172 cells and in 1 of 2 primary glioma cell cultures, TNF upregulated the expression of ICAM-1 and VCAM-1, A-172 and both primary glioma cultures also shed their TNF receptors in the absence of activation by stimulating agents. Soluble p55 (sp55) receptors, but not soluble p75 (sp75) receptors, were found to reduce the TNF induced VCAM-1 and ICAM-1 expression in both the glioma cell line and the primary cell culture. Immunostaining of malignant glioma sections confirmed the presence of soluble TNFR and adhesion molecule expression in glioma cells in situ. These data suggest that soluble TNF receptors may play a role in the mechanism by which malignant gliomas downregulate the effects of infiltrating immune-competent cells.
Insights
Soluble TNF receptors influence malignant glioma cell adhesion molecule expression. Soluble p55 receptors, but not p75, reduce tumor necrosis factor-alpha induced ICAM-1 and VCAM-1 upregulation in gliomas.
Area of Science:
- Neuro-oncology
- Immunology
- Molecular Biology
Background:
- Malignant gliomas exhibit complex interactions with the immune system.
- Tumor necrosis factor-alpha (TNF) and its receptors (TNFR) are key mediators in cellular communication and immune responses.
- Understanding adhesion molecule regulation in gliomas is crucial for therapeutic strategies.
Purpose of the Study:
- To investigate the role of TNF and soluble TNFR in regulating adhesion molecule expression (ICAM-1, VCAM-1) in malignant glioma cells.
- To determine the differential effects of p55 and p75 soluble TNF receptors on glioma cell adhesion molecule expression.
- To examine the in situ expression of soluble TNFR and adhesion molecules in glioma tissues.
Main Methods:
- Cultured malignant glioma cell lines (A-172) and primary glioblastoma cultures (LA-492, LA-567) were used.
- Expression of TNF receptor transcripts and proteins was analyzed.
- Upregulation of ICAM-1 and VCAM-1 by TNF was assessed.
- The effect of soluble p55 (sp55) and p75 (sp75) TNFR on TNF-induced adhesion molecule expression was evaluated.
- Immunostaining was performed on malignant glioma tissue sections.
Main Results:
- Glioma cells expressed varying levels of p55 and p75 TNFR.
- TNF upregulated ICAM-1 and VCAM-1 expression in most tested glioma cells.
- Glioma cells shed TNF receptors independently of stimulation.
- Soluble p55 TNFR, but not sp75 TNFR, inhibited TNF-induced ICAM-1 and VCAM-1 expression.
- Soluble TNFR and adhesion molecules were confirmed in glioma cells in situ.
Conclusions:
- Soluble p55 TNFR may downregulate the effects of immune cells infiltrating malignant gliomas.
- These findings highlight a potential mechanism by which gliomas evade immune surveillance.
- Targeting soluble TNF receptors could offer novel therapeutic avenues for malignant gliomas.