gms | German Medical Science

Objective: Although surgery and radiotherapy are effective in treating the majority of meningiomas a subset of them remains a therapeutic challenge. Radio- and chemoresistance of high-grade meningiomas have been proposed to be associated with the presence of so-called meningioma stem cells (MSC). Due to persisting uncertainty about phenotypic/functional characteristics of MSC their role in promoting meningiomas malignant progression remains to be proven. Our study aims comparing low- and high-grade meningiomas with respect to the presence of MSCs and their biological characteristics such as unlimited self-renewal, multipotency, proliferative capacity and tumor-initiating potential.

Method: Tissue samples of newly diagnosed (one WHO°I, two WHO°III case) and one recurrent case (WHO°III) of meningioma were processed within 20 minutes after resection to isolate MSCs using Brain Tumor Dissociation kit (MiltenyiBiotec). Primary cultures of MSCs were maintained in NeuroBasal medium containing B27 Supplement (Invitrogen) either with or without growth factors bFGF and EGF (10 and 20 ng/mL, resp.). Proliferation and self-renewal were reevaluated by using theBrdU incorporation (Cell Signaling Technol. Inc.), or limiting dilution assay. The results of limiting dilution assay were analyzed using the ELDA software. Multipotency was assessed by means of immunofluorescence staining for phenotypic markers of stem cells or differentiated progenies. Tumor-initiating ability was evaluated in an orthotopic mouse model.

Results: MSCs could be isolated from all four meningiomas regardless of their grade. MCSs derived from either low-grade or malignant meningiomas could be maintained for more than 6 consecutive passages either in the presence or absence of bFGF/EGF. MSCs showed no apparent morphologic or phenotypic changes indicative of differentiation in response to bFGF/EGF withdrawal or addition of fetal calf serum, stimuli that induce differentiation in glioma stem cells. MCSs derived from either low-grade or malignant meningiomas proved capable of continuous self-renewal, which is the key property of cancer stem cells. No apparent correlation between the origin of MSCs (low-/high-grade meningioma), propensity to self-renewal and tumorigenic potential was found.

Conclusions: The presence of MSCs per se may be insufficient to predict clinical response in malignant meningiomas. Further characterization of MSCs is needed to clarify their role in treatment-refractory meningiomas.