Expression neurotropher Faktoren im Vestibularisschwannom - eine Übersicht

Zusammenfassung

Das Vestibularisschwannom (Akustikusneurinom) ist ein in der Regel langsam wachsender, gutartiger Tumor, der aus den Schwann-Zellen des VIII. Hirnnervs hervorgeht. Für die Entstehung des Vestibularisschwannoms werden eine Reihe genetischer Faktoren diskutiert. Neben diesen molekularen Defekten deutet vieles darauf hin, dass das bemerkenswert variable Wachstumsverhalten der Vestibularisschwannome zusätzlich durch mitogene Stimuli gesteuert wird. Die unterschiedliche Expression neurotropher Faktoren im Gewebe des Vestibularisschwannoms stellt einen der möglichen Modulatoren dar, die auf die Entstehung und das Wachstum dieser Tumoren Einfluss nehmen könnten. Die Ergebnisse immunhistochemischer Untersuchungen belegen die Überexpression von Transforming Growth Factor-β (TGF-β) und Glial Cell Line-Derived Neurotrophic Factor (GDNF) im Vestibularisschwannom und liefern durch den Nachweis einer Coexpression Hinweise auf mögliche synergistische Interaktionen dieser beiden Nervenwachstumsfaktoren. Auch eine Reihe weiterer neurotropher Faktoren wie Nerve Growth Factor (NGF), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Neuregulin (NRG) und Erythropoetin (EPO) werden im Vestibularisschwannom exprimiert und scheinen für das biologische und klinische Verhalten dieses Tumors von Bedeutung zu sein. Die vorliegende Arbeit gibt einen Überblick über das Expressionsmuster der einzelnen neurotrophen Faktoren, deren biologische Eigenschaften und Charakteristika sowie deren Rolle im Vestibularisschwannom.

Abstract

The vestibular schwannoma is a benign, slow-growing neoplasm that originates from the neurolemmal sheath of the vestibular branch of the VIIIth cranial nerve. This tumor entity accounts for 6 % of all intracranial tumors and the annual incidence of newly diagnosed vestibular schwannoma is reported as 13 per million. The molecular pathogenesis of both sporadic vestibular schwannoma and those occurring in neurofibromatosis type II appears to be associated with an aberration of a tumor suppressor gene on chromosome 22q12. The biological background for the various growth patterns of vestibular schwannoma is, however, largely unknown. This differing clinical and biological behaviour of vestibular schwannoma may be explained by the presence of neurotrophic factors. The results of recent immunohistochemical studies demonstrate the co-expression of transforming growth factor (TGF)-β 1 and glial cell line-derived neurotrophic factor (GDNF) in vestibular schwannoma and suggest a trophic synergism of both neurotrophic factors in this tumor. Moreover, expression of numerous different neurotrophic factors has been shown in studies of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), neuregulin (NRG) and erythropoietin (EPO) indicating a biological role in development, maintainance or growth of vestibular schwannoma. In this article, we summarize the findings on neurotrophic factor expression and discuss their characteristics and biological role in vestibular schwannoma.

Vestibularisschwannom - Akustikusneurinom - Wachstum - Wachstumsfaktoren - neurotrophe Faktoren

Vestibular schwannoma - growth - growth factors - neurotrophic factors

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