Related Experiment Videos
Glioblastoma-associated circulating monocytes and the release of epidermal growth factor
G Fries1, A Perneczky, O Kempski
1Department of Neurosurgery and Institute for Neurosurgical Pathophysiology, Johannes Gutenberg-University Medical School, Mainz, Germany.
Abstract:
Monocytes/macrophages frequently infiltrate malignant gliomas and play a central role in the tumor-associated immune response as they process tumor antigen and present it to T-lymphocytes. Findings have accumulated that peripheral blood monocytes leaving the cerebral circulation become microglial cells and vice versa and that monocytes/macrophages may stimulate malignant tumor growth by some unknown mechanism. Most malignant gliomas express growth factor receptors, for example epidermal growth factor receptor (EGFR). The aim of this study was to determine whether peripheral blood monocytes of glioma patients release EGF, the appropriate ligand of gliomacell membrane-bound EGFR. Long-term cultured peripheral blood monocytes from 14 patients with malignant gliomas were compared to those from 12 controls (seven with nontumorous disease and five healthy individuals). Using an enzyme-linked immunosorbent assay for EGF, the EGF content of cell culture supernatants was determined at Days 7, 21, and 100 of culture. The EGF content (mean +/- standard error) of supernatants was 5.9 +/- 0.2 pg/ml/10(3) glioma monocytes versus 1.3 +/- 0.1 pg/ml/10(3) control monocytes at Day 7 of culture, 22.9 +/- 0.8 pg/ml/10(3) glioma monocytes versus 1.8 +/- 0.9 pg/ml/10(3) control monocytes at Day 21 of culture, and 23.4 +/- 0.7 pg/ml/10(3) glioma monocytes, and below detection levels for control monocytes at Day 100 of culture. Steroid treatment of glioma patients did not influence the EGF release of cultured monocytes. These data indicate that glioblastoma-associated peripheral blood monocytes may be distinct from those of healthy individuals. Moreover, this study indicates that subtypes of glioma-associated peripheral blood monocytes may support immunosuppression and promote growth of malignant glioma by releasing unusually high amounts of EGF.
Insights
Peripheral blood monocytes from glioma patients release significantly more epidermal growth factor (EGF) than those from healthy individuals. This suggests these monocytes may promote malignant glioma growth and immune suppression.
Area of Science:
- Immunology
- Neuro-oncology
- Cell Biology
Background:
- Monocytes/macrophages are key immune cells in malignant gliomas, influencing tumor growth and immune responses.
- Malignant gliomas often express epidermal growth factor receptors (EGFR).
- Peripheral blood monocytes can differentiate into microglia within the brain.
Purpose of the Study:
- To investigate if peripheral blood monocytes from glioma patients release epidermal growth factor (EGF).
- To determine if EGF release differs between monocytes of glioma patients and healthy controls.
- To explore the potential role of monocyte-derived EGF in glioma progression.
Main Methods:
- Long-term culture of peripheral blood monocytes from 14 malignant glioma patients and 12 controls.
- Quantification of EGF in cell culture supernatants using enzyme-linked immunosorbent assay (ELISA) at multiple time points (Days 7, 21, 100).
- Comparison of EGF levels between patient and control monocyte cultures.
Main Results:
- Glioma patient monocytes released substantially higher amounts of EGF compared to control monocytes at all measured time points.
- EGF levels in glioma monocyte cultures increased significantly over time.
- Control monocyte EGF levels remained low, below detection limits by Day 100.
Conclusions:
- Peripheral blood monocytes associated with malignant gliomas exhibit distinct characteristics compared to those from healthy individuals.
- Elevated EGF release by glioma-associated monocytes may contribute to tumor growth and immune evasion.
- These findings highlight a potential mechanism by which monocytes support malignant glioma progression.