MR-03 * MicroRNA PROFILE OF MIGRATING GLIOBLASTOMA CELLS KEPT IN STEM CELL MEDIUM

Abstract

BACKGROUND: The pronounced migration potential of tumor cells in glioblastomas (GBMs) results in infiltration of the surrounding brain. This prevents surgical removal leading to inevitable tumor recurrence. The migrating tumor cells are therefore crucial to target by other means in order to cure GBM patients. MicroRNAs have been suggested as a novel type of targets in cancer circumventing known resistance mechanisms. The aim of the present study therefore was to identify novel microRNA targets present in migrating GBM cells. In order to preserve the cancer stem cell phenotype in our studies, we developed a migration assay using serum-free so-called stem cell medium. METHODS: The migration assay was established by placing GBM spheroids on a coated surface followed by migration speed measurements using time-lapse microscopy. Five patient-derived GBM spheroid cultures and three commercial GBM cell lines were used. All culturing was performed in serum-free medium. At time-points of high migration speed, the migrating tumor cells were isolated and prepared for microRNA profiling using the corresponding spheroids for comparison. The microRNA profiling was performed using a Taqman OpenArray Human MicroRNA Panel. RESULTS: The microRNA profiling revealed 22 significantly deregulated microRNAs. Three microRNAs, miR-886-3p, miR-483-5p, and miR-1227 were more than 2 fold upregulated and 5 microRNAs, miR-590-5p, miR-210, miR-29b, miR-32, and miR222* were more than 2 fold downregulated. CONCLUSION: Migrating GBM cells kept in stem cell medium display a specific deregulated microRNA profile compared to non-migrating tumor cells. This suggests that targeting of microRNAs in migrating tumor cells with a preserved tumor initiating stem-like phenotype may be possible. The functional role of the deregulated microRNAs as well as the precise potential of therapeutic targeting needs further investigation.