gms | German Medical Science

Objective: As in any kind of tumor, meningioma progression is dependent on neovascularisation through intratumoral angiogenesis. VEGF-A is one of the most important angiogenic factors and thus the most promising target in anti-angiogenic treatment concepts in various types of tumors. Here the basal production and regulation of VEGF-A was studied in a series of human meningiomas in vitro.

Method: Primary cell cultures were established from more than 50 benign WHO grade I and 9 atypical WHO grade II meningiomas. VEGF-A secretion into the cell culture medium was determined under basal conditions or after treatment with various dosages of growth factors (TGF-beta1, TGF-alpha, PDGF-BB, IL-6), hormone analogues (octreotide, dexamethasone) and cobalt chloride, which mimics hypoxic conditions. Secreted VEGF-A isoforms were measured by ELISA.

Results: In primary culture, the basal VEGF-A secretion by meningioma cells was very heterogeneous (12 to 1,056 pg/ml/24h) and no significant difference was observed between benign and atypical meningiomas. TGF-beta1 significantly stimulated VEGF-A production in time and dose dependent manner in all meningiomas studied, TGF-alpha induced VEGF-A release in about half of the meningiomas investigated. IL-6, PDGF-BB and the somatostatin analogue octreotide had no or in few cases significant inhibitory effects on VEGF-A production. Hypoxia-mimicking conditions (cobalt chloride treatment) induced a significant rise in VEGF-A in all meningioma cell cultures studied. The synthetic glucocorticoid dexamethasone strongly suppressed basal and stimulated (TGF-beta1, TGF-alpha, cobalt chloride) VEGF-A secretion in nearly all cultures investigated.

Conclusions: The basal production of VEGF-A by meningiomas is highly variable and is not only stimulated by hypoxia but also by growth factors (TGF-beta1, TGF-alpha) which have been reported to be produced by meningiomas and may thus influence intratumoral VEGF-A release in auto-/paracrine manner. The complex regulation of VEGF-A production through different mechanisms suggests that anti-angiogenic treatment concepts in menigiomas should be focused on blocking the action of VEGF-A receptors rather than on suppressing VEGF-A production.