Introduction: In contrast to external beam radiation therapy (EBRT), where small doses of radiation is delivered to a large treatment area, brachytherapy involves the direct implant of radiation sources into a tumor bed or resection cavity to deliver radiation to a focal target. Migration of tumor away from this focal target may facilitate resistance to brachytherapy. While the molecular mechanism mediating chemotaxis from noxious chemicals is well-established, it remains unclear whether tumor cells harbor intrinsic circuitry that allow migration away from focal radiation sources. Here, we examined this question using glioblastoma cells as a model.
Methods: Glioblastoma migration relative to 131Cs seeds extracted from GammaTiles was monitored in real time using time-lapse microscopy surveillance of green fluorescent protein labelled U251 glioma cells imbedded in a two-dimensional polyacrylamide (PA) gel coated with collagen. Migration and proliferation of cells were tracked computationally at a single cell level as a function of the cumulative radiation dose of brachytherapy.
Results: Cell death was observed for glioblastoma cells exposed to > 30 Gy of 131Cs radiation. For cells receiving sub-lethal dose radiation, cell migration speed (~1 µm2/min) decreases exponentially with increasing radiation exposure (reduced to ~0.3 µm2/min at the exposed dose of 20 Gy). Moreover, viable cells exhibit propensity to migrate away from the 131Cs seed (85% cells migrated away from the seeds with the mean forward migration indices of 0.1, p = 0.0017 relative to expected migration pattern predicted based on non-directional, random migration. Moreover, tracking of individual cells show that cells migrating toward the 131Cs radiation are more likely to undergo cell death relative to those that migrated away from the radiation source.
Conclusion : These findings suggest a previously undescribed cellular behavior that we termed radio-taxis, or cellular migration away from a fixed, focal source of radiation, which confer resistance to brachytherapy.
.jpg)
