Irradiation and Taxol treatment result in non-monotonous, dose-dependent changes in the motility of glioblastoma cells

Objective: Three-dimensional conformal radiotherapy, stereotactic radiosurgery and concurrent chemoradiotherapy are among the most important postoperative therapeutic measures in the treatment of malignant gliomas. We investigated in vitro how these modalities affect cell motility, a key factor in tumor invasiveness and malignancy. Methods: A highly motile glioblastoma cell line was exposed to clinically relevant (2-20 Gy) radiation doses. Some cultures were also subjected to radiosensitizing treatment, in which 5 and 10 nM Taxol was added to the medium for 2 h before the irradiation. The surviving cell fraction was continuously monitored during a 3 day-long time period using an automatized scanning videomicroscope system. Cell motility on a two-dimensional substrate was analyzed by following a large population of cells in each culture. Average velocities, their distribution within the population and persistence of migration were calculated from the cell trajectories. Results: Irradiation increases both the persistence of migration and the heterogeneity of the cell population. Moreover, it results in a non-monotonous alteration of cell motility: While > 10 Gy doses impair motion, exposure to 2 Gy increases velocities by 20%. Taxol treatment reduced the motility of irradiated cells, while slightly increased the velocities of non-irradiated cells. We thus show that - at least for certain glioblastoma cells - both irradiation and Taxol treatment can substantially and synergistically influence cell motility. Conclusions: High grade gliomas are characterized by bad prognosis and poor response to therapy. The unexpected motogenic effect of low-dose radiation and paclitaxel treatments highlight the importance of similar investigations to develop more effective clinical treatments.