gms | German Medical Science

Objective: Meningiomas are characterized by their slowly displacing growth from the meninges and their usually benign clinical behavior. However, under conditions that have not yet been fully elucidated, even these can exhibit malignant progression with deletions effects. It is known that their suppressive growth leads to an increase in intracranial pressure (ICP), which in turn is blamed for many of the unspecific symptoms of meningeal disease. This study is the first to investigate the role of ICP in the possible malignancy.

Methods: In this study a special culture system was developed which allowed the cultivation of different primary meningioma cell cultures (PMCs, n=3) under different pressures (5, 15, 20, 25 and 35 mmHg). The analysis of the cells was performed after 4, 7 and 14 days by immunocytochemical staining against meningioma specific (vimentin, EMA, nestin) and stem cell specific antigens (SOX2, OCT4, NANOG) as well as quantitative polymerase chain reaction (qPCR).

Results: It was shown that the gene expressions SOX2 (R^{20 mmHg}_7d=8.11; R^{25 mmHg}_7d =224.88; R^{20 mmHg}_14d=491.98; R^{25 mmHg}_14d =303.35), OCT4 (R^{20 mmHg}_7d=611.29; R^{25 mmHg}_7d =2462.22; R^{20 mmHg}_14d=12.34; R^{25 mmHg}_14d =0.13) after 7 and 14 days as well as NANOG (R^{20 mmHg}_4d=4.42; R^{25 mmHg}_4d =37.42) after 4 days from a cultivation below 20 mmHg were strongly increased compared to the physiological brain pressure (15 mmHg). In immunocytochemical analysis we found elevated levels of positive cells for SOX2, NANOG and nestin in the study period. It was also noticeable that the meningioma-specific marker EMA was significantly less expressed when cultivated above 20 or 25 mmHg.

Conclusion: We were able to cultivate meningioma cells under different pressure conditions with the help of hydrostatic pressure. Moreover, we observed that cell cultivation between 20-25 mmHg for at least 7 days induced clearly dedifferentiating processes towards stem cell properties. This increase in the stem cell pool could be a possible factor that promotes the malignant transformation of a tumor.