Radiation therapy is one of standard treatment for
malignant glioma after surgery. The microenvironment after irradiation is considered not to be suitable for the survival of
tumor cells (
tumor bed effect). This study investigated whether the effect of changes in the microenvironment of parenchymal brain tissue caused by
radiotherapy affect the recurrence and progression of
glioma. 65-Gy irradiation had been applied to the right hemisphere of Fisher rats. After 3 months from irradiation, we extracted
RNA and
protein from the irradiated rat brain. To study effects of
proteins extracted from the brains, we performed
WST-8 assay and tube formation assay in vitro.
Cytokine production were investigated for qPCR. Additionally, we transplanted
glioma cell into the irradiated and
sham animals and the median survival time of F98 transplanted rats was also examined in vivo. Immunohistochemical analyses and invasiveness of implanted
tumor were evaluated. X-ray irradiation promoted the secretion of
cytokines such as CXCL12,
VEGF-A, TGF-β1 and TNFα from the irradiated brain.
Proteins extracted from the irradiated brain promoted the proliferation and angiogenic activity of F98
glioma cells.
Glioma cells implanted in the irradiated brains showed significantly high proliferation, angiogenesis and invasive ability, and the post-irradiation F98
tumor-implanted rats showed a shorter median survival time compared to the
Sham-irradiation group. The current study suggests that the microenvironment around the brain tissue in the chronic phase after exposure to X-ray radiation becomes suitable for
glioma cell growth and invasion.