Abstract 3945: Inhibition of MMP2 expression enhances the efficacy of radiation therapy for a murine astrocytoma

Radiation therapy (RT) remains the front-line treatment for high-grade gliomas; however, tumor recurrence remains the main obstacle for the clinical success of RT. Using a murine astrocytoma tumor cell line, ALTS1C1, we have previously shown that RT can effectively reduce primary tumor volume and increase mice surviving time, but the mice eventually died associated with increased tumor infiltration. In this study, we explore the role of MMP2 (Matrix metalloproteinase-2), a reported molecule associated with brain tumor invasion, on ALTS1C1 tumor response to RT. In this study, the MMP2 expression was inhibited by specific lentiviral-shRNA construct. Eight Gray of whole brain irradiation could only prolong the median survival days of brain tumor-bearing mice from 25 days to 28 days, but the inhibition of MMP2 expression by siRNA prolonged the median survival days of tumor bearing mice from 25 days to 42 days. The median survival days were further prolonged to 53 days when 8 Gy of radiation and MMP2 inhibition were concurrently applied. Immunohistochemical (IHC) results showed that the synergistic effect as a result of RT-caused vessel density decrease (inadequate vasculature) and the retardation of vessel maturation as a result of MMP2 inhibition-caused the decrease of pericyte-covered vessels (insufficient vessel function). This study provides a new treatment option for treating invasive brain tumors. (This study was supported by NHRI-EX103-10132BI and NSC 102-2314-B-007-003-MY3 grants) Citation Format: Ching-Fang Yu, Ying-Chieh Yang, Ji-Hong Hong, Chi-Shiun Chiang. Inhibition of MMP2 expression enhances the efficacy of radiation therapy for a murine astrocytoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3945. doi:10.1158/1538-7445.AM2014-3945