gms | German Medical Science

Objective: Meningiomas are considered benign tumors with slow growth rates, and the majority of these tumors histologically correspond to World Health Organization (WHO) grade I. In the majority of cases, complete surgical resection will be curative. However, a certain subset of meningiomas is biologically complex and shows a marked tendency to recur. Invasion of the adjacent bone has been shown to be a risk factor for recurrence. We hypothesized that the molecular environment provided by the bone may contribute to a more aggressive behavior in meningiomas. We therefore exposed meningioma cells cultured from resected tumor tissue to bone derived factors such as insulin-like growth factor (IGF) I&II, transforming growth factor (TGF) beta 1&2 as well as increased extracellular calcium concentrations. We subsequently observed the growth rate and bone invasiveness of the cells.

Methods: Meningioma cell cultures were 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 purity of the cultures was defined by immunofluorescent staining for epithelial membrane antigen (EMA), vimentin and GFAP. The cells were treated with IGF I&II at a concentration of 100ng/ml, TGF beta 1&2 at 10ng/ml and extracellular calcium concentration of 2, 4, and 8mmol/l. Cell growth rate was analyzed by a colorimetric cell proliferation assay. 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 and quantified by cell count.

Results: Immunofluorescent staining showed a 98% purity of the cultures obtained from surgical meningioma specimens. Treatment with increasing extracellular calcium concentrations and IGF I&II induced a significant increase of cell proliferation, whereas TGF beta 1&2 had no proliferative effects. Bone invasion was significantly enhanced in all treatment groups compared to controls.

Conclusions: Our data shows that bone derived factors induce proliferation and invasive potential in meningioma cells. This suggests that the bone matrix provides a permissive environment for a more aggressive biological phenotype in meningiomas.