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http://dx.doi.org/10.4196/kjpp.2011.15.4.211

Thrombin-induced Migration and Matrix Metalloproteinase-9 Expression Are Regulated by MAPK and PI3K Pathways in C6 Glioma Cells  

Kim, Ji-Young (Department of Pharmacology, College of Medicine, Kangwon National University)
Lee, Jae-Won (Department of Pharmacology, College of Medicine, Kangwon National University)
Kim, Song-In (Department of Pharmacology, College of Medicine, Kangwon National University)
Choi, Yong-Joon (Department of Pharmacology, College of Medicine, Kangwon National University)
Lee, Won-Ki (Department of Pharmacology, College of Medicine, Kangwon National University)
Jeong, Myung-Ja (Department of Pharmacology, College of Medicine, Kangwon National University)
Cha, Sang-Hoon (Department of System Immunology, College of Biomedical Science, Kangwon National University)
Lee, Hee-Jae (Department of Pharmacology, College of Medicine, Kangwon National University)
Chun, Wan-Joo (Department of Pharmacology, College of Medicine, Kangwon National University)
Kim, Sung-Soo (Department of Pharmacology, College of Medicine, Kangwon National University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.15, no.4, 2011 , pp. 211-216 More about this Journal
Abstract
Glioblastoma multiforme is one of the most common and aggressive tumors in central nervous system. It often possesses characteristic necrotic lesions with hemorrhages, which increase the chances of exposure to thrombin. Thrombin has been known as a regulator of MMP-9 expression and cancer cell migration. However, the effects of thrombin on glioma cells have not been clearly understood. In the present study, influences of thrombin on glioma cell migration were examined using Boyden chamber migration assay and thrombin-induced changes in MMP-9 expression were measured using zymography, semi-quantitative RT-PCR, and Western blotting. Furthermore, underlying signaling pathways by which thrombin induces MMP-9 expression were examined. Thrombin-induced migration and MMP-9 expression were significantly potentiated in the presence of wortmannin, a PI3K inhibitor, whereas MAPK inhibitors suppressed thrombin-induced migration and MMP-9 expression in C6 glioma cells. The present data strongly demonstrate that MAPK and PI3K pathways evidently regulate thrombin-induced migration and MMP-9 expression of C6 glioma cells. Therefore, the control of these pathways might be a beneficial therapeutic strategy for treatment of invasive glioblastoma multiforme.
Keywords
Thrombin; MMP-9; C6 glioma cells; MAPK; PI3K;
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