gms | German Medical Science

Objective: Cancer cells modulate their metabolism to enhance their own survival, proliferation, growth and long-term maintenance. Even in the presence of oxygen, they alter their metabolism by switching from mitochondrial respiration to anaerobic glycolysis, concomitantly increasing their glucose uptake and the fermentation of glucose to lactate. This phenomenon was first characterized by Otto Warburg in 1924 and is commonly referred to as the "Warburg effect". The extent to which this effect plays a role in the glucose metabolism and genesis of meningiomas has not been extensively investigated.

Methods: The commercially available meningioma cell line Ben Men-1 was cultured for 24h and exposed to 14 different glucose concentrations, ranging from 0 to 100 mM. Subsequently the metabolic activity and the proliferation rate were measured using MTT assays and BrdU ELISA respectively. In order to identify the glucose concentration yielding maximal proliferative and glycolytic activity, we performed a peak fitting analysis. We determined five glucose concentrations that promote maximal, minimal and optimal glycolytic activity. These five conditions were further used for immunocytochemical analysis and the cells were cultured for five passages. Doubling times, morphological changes and marker expression levels (EMA, vimentin, GLUT1, GLUT3, p-mTOR, HIF1a, NANOG, SOX2 and OCT4) were determined by immunocytochemistry.

Results: The meningioma cells' proliferative state was assessed under glucose concentrations of 0, 15, 40, 65 and 100 mM. During long-term cultivation (>four passages), cell proliferation was increased in 15 to 65 mM glucose-containing medium, in comparison to 0 to 100 mM. In the 65 mM glucose condition, the cells displayed the highest doubling time. Interestingly, cellular staining revealed significantly reduced vimentin and EMA levels in the 65 mM glucose condition. In addition, we found increased levels for p-mTOR and GLUT3 as well as high expressions of NANOG, SOX2 and OCT4 at 65 mM glucose.

Conclusion: Increasing the levels of glucose positively impacts the meningioma cells' proliferation up to a concentration of 65 mM. At this level we found an increasing expression of stem cell markers. The increased expression levels of GLUT3 and p-mTOR suggest a possible metabolic reprogramming and the expression of NANOG, SOX2 and OCT4 an ontogenic reprogramming in this context.