Increased expression levels of cysteinyl leukotriene type 1 receptors, runt-related transcription factor 1 and matrix metalloproteinase-1 in meningiomas

[Speaker] Ruenruthai Kaeopu:1
[Co-author] Laphatrada Yurasakpong:2, Kulathida Chaithirayanon:2, Wuttipong Tirakotai:3, Prasert Iampreechakul:3, Nathawut Sibmooh:1, Pornpun Vivithanaporn:1
1:Department of Pharmacology, Faculty of Science, Mahidol university, Bangkok, Thailand, 2:Department of Anatomy, Faculty of Science, Mahidol University, Bangkok, Thailand, 3:Prasat Neurological Institute, Bangkok, Thailand

Background/Objective: Meningiomas are the second most common types of primary brain tumors. Current chemotherapy drugs are not very effective and there is no standard treatment or biomarker for meningiomas. A matrix metalloproteinases type 1 (MMP-1) plays an important role in cell proliferation, angiogenesis and metastasis. Cysteinyl leukotriene receptors type 1 (CysLT1R) is associated with inflammation and cancers. Previous studies indicated that CysLT1Rs are upregulated in human colon and prostate cancers. A recent study in human Tenon's fibroblasts reported that montelukast, a selective CysL1R antagonist, inhibited TGF-Β1 induced MMP-1 release during extracellular matrix remodeling. Runt-related transcription factor 1 (RUNX1) is associated with breast cancer progression and metastasis. RUNX1 is also regulated MMP-1 expression in U-87 MG glioblastoma cells. Herein, we investigated the expression of cysteinyl leukotriene type 1 receptors, RUNX1 and MMP-1 in human meningioma tissues.
Methods: Meningiomas and normal adjacent dura tissues were collected from Prasat Neurological Institute, Bangkok, Thailand. Gene expression of CysLT1R, RUNX1, and MMP-1 were measured using real time RT-PCR. Data were presented as the median with interquartile range and analyzed by Mann Whitney U test. Immunoreactivity of CysLT1R, RUNX1 and MMP-1 were performed by using immunoperxoidase method.
Results: The average age of patients is 50 years old. Meningioma tissues (n=20) showed significantly higher expression of CysLT1R {5.43 (3.96, 20.00) vs 0.41 (0.27, 2.80)}, RUNX1 {23.92 (6.11, 22.79) vs 5.36 (0.28, 6.17)} and MMP-1 {4.85 (3.84, 7.98) vs 0.38 (0.24, 2.62)} compared to normal adjacent dura tissues (n=20). Immunohistochemistry staining showed CysLT1R, RUNX1 and MMP-1 expressions in cytoplasm of tumor cells in meningioma tissues while no positive staining was found in normal adjacent dura tissues.
Conclusion: These results suggested the importance of CysLT1R, RUNX1 and MMP-1 in meningioma pathogenesis. Therefore, levels of CysLT1R, MMP-1 and RUNX1 could be used as potential biomarkers of prognosis for meningioma and inhibition of CysLT1R by leukotriene receptor antagonists could be a novel target for meningioma treatment.
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