Role of microglial hypoxia-inducible factor-1 (HIF-1) in growth and radiation response of glioma

Abstract

Glioma is the most common type of malignant tumors in the central nervous system. Radiotherapy is current frontline treatment modality of glioma, however poor radioresponse is an obstacle to success of glioma therapy. Radioresponse depends on not only intrinsic tumor characteristics but also extrinsic tumor microenvironment. Due to radiation-induced tumor hypoxia, macrophages are recruited into irradiated glioma region and cause tumor radioresistance by enhancing vascular regrowth. In this thesis, we hypothesized that HIF-1 in microglia regulates glioma growth and its recurrence after radiation by modulating tumor microenvironment. To test our hypothesis, we measured GL261-Luc glioma growth either before or after x-ray irradiation through orthotopic glioma mouse model. Tumor microenvironment, including hypoxia, vessel and microglia, was also examined by immunofluorescence staining. We found that the growth of gliomas in myeloid-specific Hif-1α knockout mice was analogous to that of WT mice either before or after irradiating x-ray. Furthermore, there were no significant differences in tumor microenvironment between two groups either before or after irradiation. In conclusion, our results indicate that myeloid HIF-1 is independent on growth and radioresponse of glioma.