Expressions of glia maturation factor-β by tumor cells and endothelia correlate with neovascularization and poor prognosis in human glioma
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Xiao-yan Kuang1,2,*, Xue-feng Jiang1,2,*, Cong Chen1,2, Xiao-rui Su1,2, Yu Shi1,2, Jin-rong Wu1,2, Peng Zhang1,2, Xin-li Zhang1,2,3, You-hong Cui1,2, Yi-fang Ping1,2, Xiu-wu Bian1,2,4
1Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China
2Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China
3Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA, USA
4Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China
*These authors have contributed equally to the study
Xiu-wu Bian, email: [email protected]
Yi-fang Ping, email: [email protected]
Keywords: glia maturation factor-β, glioma, neovascularization, prognosis
Received: March 17, 2015 Accepted: October 13, 2015 Published: October 26, 2015
Glia maturation factor-β (GMF-β) has been reported to promote glial differentiation, and act as a negative prognostic indicator in certain cancers. However, its roles in glioma progression remain unclear. Since neurogenesis and vasculogenesis were proved to share some common regulators during gliomagenesis, we aim to explore the potential impact of GMF-β on tumor neovascularization and patient survival in glioma. In this study, we first detected GMF-β expression not only in tumor cells but also in microvascular endothelia by double immunohistochemical staining. Both tumoral and endothelial GMF-β expression levels were positively correlated with tumor grade and microvessel density (MVD), while negatively associated with poor prognoses of the patients. Interestingly, multivariate analysis demonstrated that endothelial GMF-β expression level was the only independent predictor of progression-free and overall survival of glioma patients. The results of in vitro angiogenesis assay showed that GMF-β knockdown significantly inhibited tubulogenesis of human U87 glioblastoma cells. Furthermore, GMF-β knockdown suppressed tumor growth and the formation of human-CD31 positive (glioma cell-derived) microvessels in a mouse orthotopic U87 glioma model. Our results demonstrated that GMF-β is an important player in glioma progression via promoting neovascularization. GMF-β may therefore be a novel prognostic marker as well as a potential therapeutic target for glioma.
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