gms | German Medical Science

Objective: Exposure to ionizing radiation has been linked to increased tumor formation risk which has been related to the ability of such radiation to establish or modulate tumor stem cells. The existence of tumor stem cells has been demonstrated across a variety of tumor types, including meningioma.The study investigated the molecular and phenotypic changes induced in differentiated meningioma cells by ionizing radiation.

Methods: Primary meningioma cell cultures (n=3) were cultured under standard conditions. Each confluent cell layer was irradiated once with either low (1, 2, 4, 8 Gy) or high doses (10, 12, 16, 20 Gy) of radiation. The passage time, growth form and the occurrence of morphological alterations was assessed over a period of 84 days. Immunofluorescence staining of the irradiated cells was used to demonstrate expression of tumor-specific proteins (EMA, nestin, vimentin) and proteins that regulate stem cell properties (MSI1, NANOG, Oct-4, SOX2).

Results: In the low-dosage irradiated cells, generation time was reduced and 10 passages were reached within 84 days, in contrast to cells irradiated with more than 12 Gy which showed signs of necrosis and senescence. Cells irradiated with 1-8 Gy generated viable spheres. These sphere-forming cells showed consistent expression of vimentin, CD44 and EMA, with decreased Ki67 expression associated with increased ionizing radiation dosage. The cells irradiated with 1-2 Gy showed increased NANOG, SOX2 and Oct-4 expression.

Conclusion: These data suggest that ionizing radiation induces morphological and physiological changes in primary human meningioma cells under standard conditions, which are consistent with reversion to a precursor phenotype. Reprogramming of differentiated tumor cells can be triggered by low doses of radiation with corresponding initiation of an array of regulatory pathways.