Heterogenic expression of stem cell markers in patient-derived glioblastoma spheroid cultures exposed to long-term hypoxia

Abstract

Aim: To investigate the time profile of hypoxia and stem cell markers in glioblastoma spheroids of known molecular subtype. Materials & methods: Patient-derived glioblastoma spheroids were cultured up to 7 days in either 2% or 21% oxygen. Levels of proliferation (Ki-67), hypoxia (HIF-1α, CA9 and VEGF) and stem cell markers (CD133, nestin and musashi-1) were investigated by immunohistochemistry. Results: Hypoxia markers as well as CD133 and partially nestin increased in long-term hypoxia. The proliferation rate and spheroid size were highest in normoxia. Conclusion: We found differences in hypoxia and stem cell marker profiles between the patient-derived glioblastoma cultures. This heterogeneity should be taken into consideration in development of future therapeutic strategies.