Room: Exhibit Hall
Purpose: The migration of cells is a crucial step in cancer metastasis, a complex process which accounts for over 90% of cancer-related mortality. Both preclinical and retrospective clinical studies are beginning to show that radiotherapeutic doses (over 10 Gy) meant to kill cancer cells can promote metastasis by enhancing cell migration. Here we compare radiation-induced changes in the migration of a cortical neuronal cell line (HCN2) and a glioblastoma cell line (T98G) at high (20 Gy) and low (2 Gy) doses in order to elucidate the lineage-dependence as well as the dose-dependence of the pro-metastatic effect of radiation.
Methods: We used a radiotherapy-grade cell irradiator (CellRad, Faxitron) to give clinically lethal and sub-lethal doses of X Rays to HCN2 and T98G cells. We used a commercial impedance sensing device (ECISÂ®) to assess the migration of the cells following irradiation, for at least 100 hours. Phase contrast microscopy and morphometry of cells were done to corroborate the migration data.
Results: The migration of both HCN2 cortical neurons and T98G glioblastoma cells in ECIS was significantly enhanced by the high dose X-Rays (20 Gy) before radiation-induced cell death. Morphometry revealed evidence of radiation-induced cytoplasmic alterations in both cell lines. Low dose irradiation produced phases with enhanced as well as reduced migration.
Conclusion: The enhancement of migration by a radiotherapeutic dose (20 Gy) both in tumor (T98G) and non-tumor (HCN2) cells engenders the need for anti-migratory drugs to inhibit the apparent pro-metastatic effect of radiotherapy while permitting eventual tumor cell killing. This will potentially improve radiotherapy outcomes especially in glioblastomas which are currently highly invasive and resistant to chemo- and radiotherapy for reasons that are still unclear.