gms | German Medical Science

Objective: Meningiomas are primarily benign and slow-growing tumours. There are only few stable meningioma cell lines. Therefore primary cell cultures are often used for meningioma research in vitro. But those primary cell cultures change their initial phenotype within few passages and then go into senescence. This is a major problem for meningioma research. On the other hand induction of senescence may be an important tumor suppressor mechanism in benign tumors. Also senescence markers could point a way for possible recurrence biomarkers.

Method: Expression levels of 44 cell cycle regulation proteins and 92 cell surface proteins were analyzed in six primary meningioma cell cultures using real-time PCR. Significantly changed proteins were further examined in 8 additional meningiomas. Proteins were also determined using TaqMan^® Protein Assay and Western Blot.

Results: Most significant changes in cell cycle regulation protein expression in senescent cells were expected. But CDK6 expression was significantly increased in senescent meningioma cells (mean(P0)=2.22±2.29; mean(P7)=72.88±49.79; p<0.0001). The expression of several cell surface markers changed significantly in senescent cells. COL1A1, COL1A2, ITGA1, and ITGA3 levels were significantly elevated in senescent meningiomas in vitro (p<0.0001). Expression of CD163, CD74, CSF1R, HLA-DRA, IL2R4, PECAM1, and S100A8 were significantly decreased (p < 0.0001).

Conclusions: The most notable change of examined cell cycle regulation proteins was significantly increased CDK6 expression. Normally CDK6 protein levels decrease in cultured senescent cells. Therefore the role of CDK6 in meningiomas should be further analyzed. In addition, several altered cell surface proteins were identified and should be evaluated as biomarkers for recurrence and malignancy.