gms | German Medical Science

Objective: In contrast to normal mammalian cells, which use oxygen to generate energy, cancer cells use glycolysis to generate energy due to their increased metabolism. This effect has an important role in carcinogenesis and tumor progression. The extent to which this also applies to meningiomas has not yet been investigated. The aim of this study is to investigate the influence of different glucose levels during glycolysis on tumor-promoting processes in the human meningioma in vitro.

Methods: The commercially available meningioma cell line Ben Men-1 was cultured 24h in a glucose-free medium. Afterwards, the metabolic activity was measured by MTT assay and the proliferation rate by BrdU ELISA under 14 different glucose concentrations (in the range of 0 to 100 mM) after 24 hours. A peak fitting analysis was used to determine the concentrations for maximum proliferation and glycolysis activity. Subsequently, 5 concentrations were determined that promote maximum, minimum and optimal activities. The cells were seeded at a density of 6x 10⁵ cells/25cm² and further cultured under the previously defined conditions over 5 passages. Doubling times, morphological changes and marker expression (EMA, vimentin, GLUT1, GLUT3, p-mTOR, HIF1a) were determined by immunocytochemistry.

Results: Peak fitting analysis of maximum metabolic activity at glucose concentrations of 17.2 mM and 66.7 mM, maximum proliferation rates at concentrations of 18.5 mM, 35.6 mM and 57.3 mM were determined. Based on these facts, the cells were then cultured and analyzed with glucose concentrations of 0, 15, 40, 65 and 100 mM. It was found that long-term cultivation (>p4) with 0 and 100 mM glucose was not possible. Cultivation under 15–65 mM glucose concentrations for a longer period of time was possible. The cells fed with 65 mM glucose showed the fastest doubling times. The immunocytochemical characterization showed surprisingly decreasing vimentin and EMA signals in the 65 mM group in contrast to the other investigation groups. In addition, we found increased values for pmTOR and GLUT3. GLUT1 and HIF1a showed no differences between the groups.

Conclusion: Our results show that meningioma cells also respond to an increase in environmental glucose levels with an increased tumor progression. In particular, the increased expression of GLUT3 and p-mTOR suggests a possible metabolic reprogramming in this context.