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Autocrine control of human meningioma proliferation: secretion of platelet-derived growth-factor-like molecules
E F Adams1, T Todo, U M Schrell
1Department of Neurosurgery, University of Erlangen-Nuremberg, Germany.
Abstract:
We have used cell-culture techniques to investigate growth-factor production by human meningioma cells. Meningioma tissue was dispersed with collagenase and the cells grown to high density in tissue-culture flasks. The cultures were used to generate conditioned medium (MEN-CM), which was used to cultivate IMR32 cells (a human neuroblastoma line) and freshly dispersed primary meningioma cells. MEN-CM profoundly stimulated the in vitro growth of both IMR32 and meningioma cells. In addition, H3-thymidine uptake by cultured meningioma cells was increased in a dose-dependent manner by varying concentrations of MEN-CM. A neutralizing anti-body against platelet-derived growth factor (PDGF) completely abolished the stimulatory effects of MEN-CM, whereas an antibody against TGF-alpha was without effect. The mitogenic activity of MEN-CM, as assayed by promotion of H3-thymidine uptake by cultured meningioma cells, eluted from a Sephadex G-100 column in 3 peaks corresponding to molecular weights of greater than or equal to 150, 56 and 28 kDa. Our results show that proliferation of human meningiomas may be under autocrine control via secretion of PDGF-like molecules.
Insights
Human meningioma cells secrete platelet-derived growth factor (PDGF)-like molecules. These molecules stimulate meningioma cell proliferation, suggesting autocrine control in tumor growth.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Meningiomas are the most common primary tumors of the central nervous system.
- The molecular mechanisms driving meningioma proliferation are not fully understood.
Purpose of the Study:
- To investigate growth factor production by human meningioma cells.
- To determine if meningioma cell proliferation is regulated by autocrine signaling.
Main Methods:
- Cell-culture techniques were used to grow primary human meningioma cells.
- Conditioned medium (MEN-CM) from meningioma cultures was used to stimulate IMR32 neuroblastoma cells and primary meningioma cells.
- Neutralizing antibodies against platelet-derived growth factor (PDGF) and TGF-alpha were employed.
- Size exclusion chromatography (Sephadex G-100) was used to characterize the molecular weight of mitogenic factors.
Main Results:
- Conditioned medium from meningioma cells (MEN-CM) significantly stimulated the in vitro growth of both IMR32 and primary meningioma cells.
- MEN-CM increased H3-thymidine uptake in cultured meningioma cells in a dose-dependent manner.
- A neutralizing antibody against PDGF abolished the stimulatory effects of MEN-CM, while an antibody against TGF-alpha had no effect.
- Mitogenic activity in MEN-CM eluted in three peaks corresponding to molecular weights >=150 kDa, 56 kDa, and 28 kDa.
Conclusions:
- Human meningioma cells secrete PDGF-like molecules.
- These secreted PDGF-like molecules stimulate meningioma cell proliferation.
- Meningioma growth may be under autocrine control mediated by PDGF-like factors.