Related Experiment Videos
Response of low-passage human malignant gliomas in vitro to stimulation and selective inhibition of growth
I F Pollack1, M S Randall, M P Kristofik
1Department of Neurosurgery, University of Pittsburgh School of Medicine, Pennsylvania.
Abstract:
The proliferation of many nonglial tumors in vitro depends on the presence of nanomolar concentrations of one or more growth factors. To define the growth factor requirements of malignant glial tumors, the authors examined the response properties of four low-passage human malignant glioma lines to the following mitogens: epidermal growth factor (EGF), acidic and basic fibroblast growth factors (FGF's), insulin-like growth factor I (IGF-I), nerve growth factor (NGF), platelet-derived growth factor (PDGF), 12-O-tetradecanoyl-13-phorbol acetate (TPA), and serum. Each of the tumors showed increased deoxyribonucleic acid (DNA) synthesis (assessed by acid-precipitable [3H]-thymidine incorporation) in response to PDGF with a maximum effect at 50 ng/ml. Three tumors responded to EGF, three to IGF-I, two to acidic FGF, two to basic FGF, and two to TPA with maximum effects at 10, 50, 1, 1, and 10 ng/ml, respectively. None of the tumors responded to NGF. In the responsive tumors, optimum concentrations of EGF, IGF, TPA, acidic FGF, and basic FGF induced, at most, a two- to fourfold increase in [3H]-thymidine incorporation, which was only 30% to 50% of the response seen in 10% serum. In contrast, PDGF increased DNA synthesis eight- to 10-fold, equaling the effect of 10% serum. Measurements of cell proliferation also demonstrated a significant response to PDGF in each of the tumors. Appropriate concentrations of an anti-PDGF neutralizing antibody inhibited baseline DNA synthesis and proliferation in the absence of added growth factors, suggesting the possible role of PDGF in autocrine stimulation of these cells. However, this antibody produced only slight inhibition of serum-induced mitogenesis. Trapidil, an agent reported to inhibit the effects of PDGF, and polymyxin B, an inhibitor of protein kinase C, strongly inhibited baseline as well as PDGF- and serum-induced mitogenesis. It is concluded that, in the malignant gliomas studied, PDGF may be acting as a dominant mitogen to enhance DNA synthesis, and may function in autocrine stimulation. However, other factors contained in serum can also contribute to cell division.
Insights
Platelet-derived growth factor (PDGF) is a dominant mitogen for malignant glioma cells, driving DNA synthesis and proliferation. It may also play a role in autocrine stimulation, though other serum factors contribute to cell division.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Malignant glioma proliferation in vitro often depends on growth factors.
- Understanding specific growth factor requirements is crucial for targeting these tumors.
Purpose of the Study:
- To define the growth factor requirements of human malignant glioma cell lines.
- To investigate the role of platelet-derived growth factor (PDGF) in glioma cell proliferation.
Main Methods:
- Assessed DNA synthesis via [3H]-thymidine incorporation in response to various mitogens.
- Measured cell proliferation and effects of anti-PDGF antibody, trapil, and polymyxin B.
Main Results:
- PDGF significantly increased DNA synthesis and proliferation in all tested glioma lines.
- Epidermal growth factor (EGF), insulin-like growth factor I (IGF-I), and fibroblast growth factors (FGFs) showed variable responses.
- Anti-PDGF antibody suggested a role for PDGF in autocrine stimulation, while trapil and polymyxin B inhibited mitogenesis.
Conclusions:
- PDGF acts as a dominant mitogen in malignant gliomas, promoting DNA synthesis and potentially autocrine stimulation.
- Serum contains other factors that also contribute to glioma cell proliferation.