Autor: |
Tsai, Wen-Chiuan, Chen, Ying, Huang, Li-Chun, Lee, Herng-Sheng, Ma, Hsin-I, Huang, Shih-Ming, Sytwu, Huey-Kang, Hueng, Dueng-Yuan |
Zdroj: |
Journal of Neuro-Oncology; Oct2013, Vol. 114 Issue 3, p281-290, 10p |
Abstrakt: |
High-grade primary brain tumors possessed poor outcome due to invasiveness. Extracellular matrix metalloproteinase inducer (EMMPRIN) stimulates peri-tumoral fibroblasts to secrete matrix metalloproteinase and promote invasiveness. This study hypothesized that high-grade brain tumors overexpress EMMPRIN. Analyzing the public delinked database from the Gene Expression Omnibus profile, the results showed that the EMMPRIN mRNA level was higher in WHO grade IV ( n = 81) than in grade III ( n = 19, p < 0.0005) astrocytomas and non-tumor brain tissue controls ( n = 23, p < 0.00001). The results of tissue microarray-based immunohistochemical (IHC) staining revealed that EMMPRIN levels positively correlated with WHO grades for astrocytomas ( p = 0.008) and meningiomas ( p = 0.048). EMMPRIN mRNA levels in conventional glioma cell lines ( n = 36) was not less than those in glioma primary culture cells ( n = 27) and glioblastoma stem-like cells ( n = 12). The GBM8401, U87MG, and LN229 human glioma cell lines also overexpressed EMMPRIN. Hematoxylin and eosin, IHC, and immunofluorescence staining of xenografts confirmed that high-grade brain tumors overexpressed EMMPRIN. Lastly, Kaplan-Meier analysis revealed poorer survival in WHO grade IV ( n = 56) than in grade III astrocytomas ( n = 21, by log-rank test; p = 0.0001, 95 % CI: 1.842-3.053). However, in high-grade astrocytomas, there was no difference in survival between high and low EMMPRIN mRNA levels. Thus, this study identified that high-grade brain tumors overexpress EMMPRIN, which positively correlates with WHO grades in human astrocytomas and meningiomas, and suggests that EMMPRIN may be a therapeutic target of brain tumor. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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