Expressions of glia maturation factor-β by tumor cells and endothelia correlate with neovascularization and poor prognosis in human glioma

Glia maturation factor-beta (GMF-beta) 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-beta on tumor neovascularization and patient survival in glioma. In this study, we first detected GMF-beta expression not only in tumor cells but also in microvascular endothelia by double immunohistochemical staining. Both tumoral and endothelial GMF-beta 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-beta 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-beta knockdown significantly inhibited tubulogenesis of human U87 glioblastoma cells. Furthermore, GMF-beta 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-beta is an important player in glioma progression via promoting neovascularization. GMF-beta may therefore be a novel prognostic marker as well as a potential therapeutic target for glioma.