Association of Astrocyte Activation with the Response of Brain Tumor to Radiation Therapy

Astrocytes are the most abundant member of brain glial cells and have multiple roles in the central nervous system. Meanwhile, astrocytes actively respond to many neuropathological changes, including CNS tumors, such as gliomastoma (GBM) and irradiation during radiation therapy. Although many studies implicate the involvement of astrogliosis in brain tumor progression, their roles in tumor response to therapy are still unclear. Using a mouse astrocytoma cell line, ALTS1C1 transfected with luciferase in an intracranial implantation model, and immunohistochemical staining (IHC) approach to examine the development of tumor microenvironment during tumor progression, this study found that astrocyte activation, evidenced by enhanced GFAP expression, is un-evenly distributed across the tumor. Following 15 Gy of brain tumor irradiation, caspase-3 positive cells are rarely found in regions with reactive astrocytosis. This study illustrates that the activation of astrocytes creates a special niche for brain tumor to grow and protect them to the cytotoxicity of irradiation. The association of astrocyte activation with the development of radioresistance provides another option for combination trials in patients with GBM.