Radiation-enhanced hepatocyte growth factor secretion in malignant glioma cell lines.

Background Postoperative radiotherapy is the standard treatment for patients with a malignant glioma. However, a malignant glioma is radioresistant and almost always recurs, even after a high dose of radiation. A malignant glioma is characterized by its proliferation, invasion and neoangiogenesis, which can be attributed to the high levels of HGF. The scope of this study is to investigate HGF secretion by malignant glioma cells with different radiosensitivity after irradiation. Methods Three human malignant glioma cell lines (U251, U251-NG2, and BT325) were irradiated with single doses of 0, 5, 10, and 20 grays of γ-rays from a 137Cs source. Hepatocyte growth factor levels in medium were measured by ELISA at 24, 48, and 72 hours after radiation. Cell survival was measured by the proliferation-based assay (XTT assay) 7 days after irradiation. Results After a single dose radiation, the HGF levels showed a dose-dependent increase in U251, U251-NG2, and BT325 glioma cells. Both baseline and radiation-enhanced HGF levels were about 10-fold higher in BT325 compared to U251 and U251-NG2 cells. In addition, in the XTT assay, the BT325 was more radioresistant than both U251 and U251-NG2 cell lines (dose modifying factor = 1.5 and 1.6, respectively). Conclusion Irradiation-enhanced HGF secretion in all 3 tested glioma cell lines (up to 7 times basal levels). It is tempting to associate the radiation-enhanced HGF secretion with an increased angiogenic potential of the tumor, which may be a factor in radioresistance.