The main characteristic of glioma is recurrence, even after intensive multidisciplinary treatment. Studies show that enhanced invasive ability will increase the ability of tumor cells to escape from the primary tumor mass, which is a key factor contributing to tumor relapse and recurrence. In this study, we assessed the expression of MMP-2, MMP-9, two important matrix metallopeptidases that increase the invasive ability of glioma, and their suppressors, TIMP-1, TIMP-2 in glioma tissues from primary and recurrent glioma patients by immunohistochemistry. Glioma cells and nude mice were used for in vitro and in vivo studies. Results showed that the expression of MMP-2 and MMP-9 in recurrent gliomas were significantly higher than those in primary gliomas (P = 3.075 × 10-11, P = 1.510 × 10-5, respectively). We also found that radiotherapy increased the expression of MMP-9, but had no effect on MMP-2 and TIMP-1/2. With glioma cell line U251, we found that irradiation increased the expression of MMP-9 in vitro. Tumor tissues from an orthotopic xenograft model showed that after irradiation treatment, the expression of MMP-9 increased significantly in vivo. We also found that knocking down MMP-9 decreased irradiation-induced invasion obviously. Above all, we concluded that higher expressions of MMP-2/-9 indicate poor prognosis in glioma recurrence. The increased expression of MMP-9 after radiotherapy suggests that MMP-9 might be an important target in the radiosensitization of glioma.
Keywords: Glioma; MMPs; Prognosis; Radiotherapy; Relapse; TIMPs.
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