Osteopontin regulates human glioma cell invasiveness andtumor growth

• Main Authors: Hsun-Jin Jan, 詹勳錦
• Other Authors: 李宏謨
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/13125125312332456301

博士 === 臺北醫學大學 === 醫學科學研究所 === 97 === Human malignant glioma cells are characterized by invaded-growth of adjacent tissues. In this study, we demonstrated that different human glioma cells exhibit distinct capacity of invasiveness and proliferation in vitro and in vivo. Osteopontin (OPN) protein and mRNA levels correlate well with their capacity of proliferation and invasiveness. In order to understand whether OPN plays a therapeutic target to strategy of glioma treatment, glioma cells were stable expressed with specific shRNA to knockdown OPN expression, subsequently MMP-2 activity and expression were dramatically reduced. OPN-knockdown also reduced cell invasiveness and proliferation in glioma cells. In animal model, knockdown of OPN expression resulted in decreasing of tumor growth in vivo. In contrast, forced OPN expression in glioma cell with lower OPN level, we found OPN promoted cell invasiveness and proliferation in vitro and in vivo. These results suggest that OPN may serve a role in glioma cell invasiveness and proliferation. The ratio of Glial fibrillary acidic protein (GFAP) and Vimentin have been demonstrated that strong correlated with glioma malignancy. We found that OPN alters GFAP/Vimentin ratio in glioma cell lines, suggesting that OPN might regulated the differentiation state in glioma cells. We investigated that OPN regulated hypoxia inducible factor-1α(HIF-1α) expression in glioma cell lines. We have demonstrated that HIF-1α plays the pivotal role in cell invasiveness, metabolism and mitochondria membrane potential in glioma cells. In our previously studies, we demonstrated that 5-AzadC (5-Aza-2''-deoxycytidine) induced MKP-1 (Mitogrn activated protein kinase phosphatase-1) expressionin glioma cell lines. We also found that MKP-1 supressed HIF-1αexpression in human glioma cell lines. Finally, we explore that 5-AzadC reduced OPN expression, led todecrease cell invasiveness and proliferation in vitro and in vivo. Taken together, OPN signaling pathway may play an important role in glioma progression involved in cell invasiveness and tumor growth. Given 5-AzadC can regulated OPN expression in glioma cells. Furthermore, 5-AzadC may serve as a pivotal therapeutic drug in OPN-induced malignant glioma.