Abstract
Radiotherapy (RT) is a major strategy for treating brain tumors, but the relative high percentage of recurrent brain tumors after RT is frequently reported clinically and is associated with a lower cure rate. Despite many studies focus on the methods to improve the efficacy of RT for brain tumor, the alteration of the microenvironments in recurrent brain tumor after RT is still not clear. To investigate the behaviors of recurrent brain tumors after RT, we used a murine astrocytoma, ALTS1C1, growing from pre-irradiated (pre-IR) brain tissues as a pre-clinical brain tumor recurrent model. Using this model, we found that tumors grown from pre-IR brain tissues have lower microvascular density (MVD), more hypoxic and necrotic regions, and the aggregation of tumor-associated macrophages (TAMs) in hypoxic regions, which is generally called tumor bed effect (TBE). However, whether TBE would result in tumor growth delay still depends on many other factors, such as pre-IR dose, the expression of stromal-cell-derived factor-1 (SDF-1), or type of tissues. For example, using MVD, hypoxia, or necrosis as the readout for TBE, a good pre-IR dose response could be found between 8 ~ 15 Gy, but tumor growth delay was only found in 15 Gy pre-IR group. When the expression of SDF-1 by ALTS1C1 cells was suppressed by siRNA approach, the tumor growth delay in 15 Gy pre-IR group disappeared. This indicates that the growth rate of recurrent brain tumor is the result of the interplay between tumor cells and irradiated tumor microenvironments. To understand the mechanisms behind them will