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Expression of PDGF beta-receptors in human meningioma cells
J L Wang1, M Nistér, M Hermansson
1Department of Pathology, University Hospital, Uppsala, Sweden.
Abstract:
Meningioma is a generally benign tumor derived from arachnoid tissue. We have investigated the presence of functionally active PDGF-receptors on human meningioma cells in culture. Tumor samples were obtained from 3 surgically removed benign meningiomas and normal arachnoid tissue from an autopsy case. Binding studies were performed by using 125I-labelled recombinant PDGF-AA and PDGF-BB. Only 125I-PDGF-BB showed specific binding to all tumor-cell cultures after incubation of cells for 2 hr at 4 degrees C. Effects of PDGF-AA and PDGF-BB on DNA synthesis were measured as 3H-thymidine incorporation during 48 hr of labelling cells maintained in Eagle's minimum essential medium 0.5% fetal calf serum. PDGF-BB but not PDGF-AA stimulated DNA synthesis in all 3 tumor-cell cultures. Total cellular RNA was analyzed by Northern blotting and hybridization with a 32P-labelled human PDGF beta-receptor probe, and PDGF beta-receptor mRNA was found in both tumor and arachnoid cell cultures. Furthermore, PDGF beta-receptor mRNA was shown to be present in 2 meningioma biopsies and immunohistochemical staining revealed that PDGF beta-receptors are present in meningioma and arachnoid tissues in vivo. It appears that a possible way of maintaining human meningioma cell growth in vivo is through activation of PDGF beta-receptors.
Insights
Human meningioma cells possess active platelet-derived growth factor beta-receptors (PDGF-receptors). PDGF-BB stimulates DNA synthesis in these cells, suggesting a role in meningioma growth.
Area of Science:
- Neuro-oncology
- Molecular biology
- Cell biology
Background:
- Meningioma, a common primary brain tumor, originates from arachnoid tissue.
- The role of growth factors and their receptors in meningioma pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the presence and functionality of platelet-derived growth factor receptors (PDGF-receptors) on human meningioma cells.
- To determine if PDGF signaling influences meningioma cell proliferation.
Main Methods:
- Primary human meningioma and normal arachnoid cells were cultured.
- Binding studies using radiolabeled PDGF-AA and PDGF-BB.
- Assessment of DNA synthesis via 3H-thymidine incorporation.
- Analysis of PDGF beta-receptor mRNA by Northern blotting.
- Immunohistochemical staining for PDGF beta-receptors in tissue samples.
Main Results:
- Specific binding of PDGF-BB, but not PDGF-AA, was observed on cultured meningioma cells.
- PDGF-BB significantly stimulated DNA synthesis in meningioma cells.
- PDGF beta-receptor mRNA and protein were detected in both meningioma and arachnoid tissues in vitro and in vivo.
Conclusions:
- Human meningioma cells express functionally active PDGF beta-receptors.
- PDGF-BB can stimulate DNA synthesis in meningioma cells.
- PDGF-receptor activation may be a key mechanism in maintaining human meningioma cell growth in vivo.