Article
The role of PTHrP in meningioma bone invasion
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Authors
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M.A. Proescholdt
- Klinik für Neurochirurgie, Universitätsklinikum Regensburg
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E.M. Störr
- Klinik für Neurochirurgie, Universitätsklinikum Regensburg
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A. Lohmeier
- Klinik für Neurochirurgie, Universitätsklinikum Regensburg
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A. Brawanski
- Klinik für Neurochirurgie, Universitätsklinikum Regensburg
| Published: | June 4, 2012 |
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Outline
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Objective: Invasion of the adjacent bone has been shown to be a risk factor for recurrence and poor prognosis in meningiomas. However, the molecular mechanism for this process is unknown. Parathyroid hormone related protein (PTHrP) causes osteoclast activation and mediates bone metastasis in different cancer types. We hypothesized that PTHrP is also a mediator of meningioma specific bone invasion. We therefore analyzed the PTHrP expression in bone invasive and non-invasive meningiomas. In addition, we stimulated meningioma cell cultures with bone derived growth factors such as transforming growth factor (TGF) beta 1&2, which are known to induce PTHrP expression. Using RNA interference, PTHrP expression was knocked down. Subsequently, we observed the bone invasiveness utilizing a tumor - bone co-culture assay.
Methods: 66 meningioma samples (30 with, 36 without bone invasion) were analyzed for PTHrP expression by immunohistochemistry, Western Blot and RTPCR. Meningioma cell culture was established from 21 tumors resected from 7 male (33.4%) and 14 female (66.6%) patients, with a mean age of 62.7 years (range: 43–82 years). The cell cultures were treated with TGF beta 1&2 at 10 ng/ml. Gene knockdown was performed by transfection with a PTHrP siRNA construct utilizing lipofectamine as transfection reagent. As control served a non specific sequence siRNA. Bone invasion was analyzed by co-cultivation of meningioma cells with neonatal mouse calvariae. The invading cells were visualized with immunofluorescent staining for human HLA.
Results: The bone invasive meningioma samples showed significant higher PTHrP expression both at the mRNA and the protein level. Treatment with TGF beta 1&2 strongly enhanced meningioma bone invasion in vitro which was again significantly reduced by PTHrP knockdown.
Conclusions: Our data show that that PTHrP is overexpressed in bone invasive meningiomas. Induction and gene knockdown experiments indicate that PTHrP plays an important functional role in menigioma bone invasion.
