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TGF-B2 and soluble p55 TNFR modulate VCAM-1 expression in glioma cells and brain derived endothelial cells
T C Chen1, D R Hinton, V W Yong
1Department of Pathology, School of Medicine, University of Southern California, Los Angeles 90033, USA.
Abstract:
Transforming growth factor beta-2 (TGF-B2) is secreted by glioma cells and is known to decrease leukocyte-endothelium interaction. TGF-B2 alone and in conjunction with soluble tumor necrosis factor (TNF) p55 receptor, was found to decrease the expression of TNF induced VCAM-1 on the malignant glioma cell line A-172 and human cerebral microvessel endothelial (CNS-EC) cells. Co-culture of A-172 glioma cells led to a decrease in VCAM-1 expression; this effect on CNS-EC in co-culture could be simulated by glioma supernatant alone. These results suggest that malignant gliomas, by secreting TGF-B2 and releasing soluble TNF receptors, modulate adhesion molecules.
Insights
Malignant gliomas secrete transforming growth factor beta-2 (TGF-B2) and soluble tumor necrosis factor (TNF) receptors, which reduce VCAM-1 expression on brain endothelial cells. This suggests gliomas actively modulate the neurovascular environment.
Area of Science:
- Neuro-oncology
- Immunology
- Cellular Biology
Background:
- Malignant gliomas secrete factors influencing the tumor microenvironment.
- Leukocyte-endothelium interactions are critical in neuroinflammation and tumor progression.
- Transforming growth factor beta-2 (TGF-B2) is a known immunosuppressive cytokine secreted by gliomas.
Purpose of the Study:
- To investigate the role of TGF-B2 and soluble TNF receptors in modulating VCAM-1 expression in malignant glioma models.
- To determine if glioma cells or their secreted factors impact endothelial cell adhesion molecule expression.
Main Methods:
- Utilized malignant glioma cell line A-172 and human cerebral microvessel endothelial (CNS-EC) cells.
- Performed co-culture experiments with glioma cells and CNS-EC.
- Analyzed VCAM-1 expression following treatment with TGF-B2, soluble TNF p55 receptor, and glioma cell supernatant.
Main Results:
- TGF-B2 alone and with soluble TNF p55 receptor decreased TNF-induced VCAM-1 expression on A-172 and CNS-EC cells.
- Co-culture with A-172 glioma cells reduced VCAM-1 expression on CNS-EC.
- Glioma cell supernatant alone mimicked the VCAM-1 downregulatory effect observed in co-culture.
Conclusions:
- Malignant gliomas secrete TGF-B2 and soluble TNF receptors that downregulate VCAM-1 expression on endothelial cells.
- These secreted factors contribute to the modulation of leukocyte-endothelium interactions in the glioma microenvironment.
- Glioma-derived factors play a significant role in altering the adhesion molecule profile of the neurovasculature.