Artikel
Overexpression and anti-apoptotic effects of midkine in intracranial meningiomas
Überexpression und anti-apoptotische Effekte von Midkine bei intrakraniellen Meningeomen
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Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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Objective: Meningiomas are the second most common tumours of the central nervous system. Most of the meningiomas grow slowly whereas atypical and anaplastic meningiomas show an aggressive biological behaviour and a high risk of recurrence. Overexpression of growth factors is often considered to be a cause of carcinogenesis. Midkine and pleiotrophin are heparin-binding growth factors that promote growth, survival, migration and differentiation of various target cells. They are expressed during embryogenesis or early postnatus but rarely in the adult.
Results: We could show that in relation to normal dura and arachnoidal tissue midkine was overexpressed in meningiomas on mRNA and protein level whereas pleiotrophin was not. Thereby not only the intact form but also the truncated form of midkine could be observed. The expression of midkine receptors was variable in different samples. Midkine stimulation of cultivated meningioma cells induced phosphorylation of the kinase, whereas no increase in phosphorylation of p42/44 MAPK and p38 MAPK could be detected. While midkine did not influence the proliferation of meningioma cells in vitro, it protected meningioma cells against camptothecin-mediated apoptosis through down-regulation of caspase-3 activity and up-regulation of Bcl-2 expression.
Conclusions: These findings provide evidence for the overexpression of midkine in meningiomas which appears to be a malignant de-differentiation factor of meningiomas and favors tumour growth by its anti-apoptotic effect.