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Control of meningioma cell growth by platelet-derived growth factor (PDGF)
A Mauro1, A Di Sapio, C Mocellini
12nd Department of Neurology, University of Turin, Italy.
Abstract:
We have examined the possible involvement of PDGF and PDGF receptors in the growth control of five meningiomas, analyzing the biopsy specimens and the primary cultures derived from the same tumors. Light and electron microscopy demonstrated that MAbs against PDGF beta-receptors immunodecorate meningioma cells in vivo and in vitro, while those against alpha-receptors gave negative results. The effects of PDGF isoforms AA, AB, BB and of PDGF neutralizing antibodies on meningioma cultures were examined using [3H]thymidine incorporation analysis. Only with PDGF-AB and -BB a mitogenic effect was observed, while PDGF-neutralizing antibodies produced a reduction of [3H]thymidine incorporation. The production of PDGF-like growth factors by meningioma cells was tested analyzing the effects of meningioma culture-conditioned media on the growth of Swiss 3T3 cells. In all cases meningioma conditioned media stimulated the in vitro growth of 3T3 fibroblasts and this stimulatory effect was strongly reduced by PDGF-neutralizing antibodies. Furthermore, Northern blot analysis demonstrated expression of c-sis/PDGF-B and PDGF beta-receptors mRNA in all meningioma biopsies and in all the derived cultures. Our results provide strong evidence that PDGF-B chain and PDGF beta-receptors are involved in growth control mechanisms of human meningiomas through autocrine and/or paracrine mechanisms.
Insights
Platelet-derived growth factor (PDGF) and its beta-receptors are implicated in human meningioma growth. These findings suggest PDGF-B and beta-receptors play a role in tumor development via autocrine or paracrine signaling.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Cell Signaling
Background:
- Meningiomas are primary tumors of the central nervous system.
- The molecular mechanisms driving meningioma growth are not fully understood.
- Platelet-derived growth factor (PDGF) and its receptors are known regulators of cell growth.
Purpose of the Study:
- To investigate the role of PDGF and its receptors in the growth control of human meningiomas.
- To determine if PDGF signaling pathways are active in meningioma cells.
- To explore the potential for autocrine or paracrine PDGF signaling in meningiomas.
Main Methods:
- Immunohistochemistry and immunofluorescence on meningioma biopsy specimens and primary cultures using monoclonal antibodies (MAbs) against PDGF alpha- and beta-receptors.
- Assessment of PDGF isoform (AA, AB, BB) effects on meningioma cell proliferation using [3H]thymidine incorporation assays.
- Evaluation of PDGF-neutralizing antibodies on meningioma cell proliferation.
- Analysis of conditioned media from meningioma cultures for PDGF-like growth factors by assessing their effect on Swiss 3T3 fibroblast growth.
- Northern blot analysis to detect messenger RNA (mRNA) expression of c-sis/PDGF-B and PDGF beta-receptors.
Main Results:
- PDGF beta-receptors were detected on meningioma cells in vivo and in vitro, while alpha-receptors were not.
- PDGF-AB and -BB isoforms stimulated meningioma cell proliferation, and neutralizing antibodies reduced it.
- Meningioma conditioned media promoted 3T3 fibroblast growth, an effect reduced by PDGF-neutralizing antibodies.
- Expression of c-sis/PDGF-B and PDGF beta-receptors mRNA was confirmed in all meningioma samples and cultures.
Conclusions:
- PDGF-B chain and PDGF beta-receptors are significantly involved in the growth control of human meningiomas.
- Autocrine and/or paracrine mechanisms mediated by PDGF signaling contribute to meningioma pathogenesis.
- Targeting PDGF signaling pathways may offer therapeutic strategies for meningiomas.