title: Expressions of glia maturation factor-β by tumor cells and endothelia correlate with neovascularization and poor prognosis in human glioma.
abstract: 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.
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Kuang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Jiang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Su
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Wu
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.|Division of Growth and Development and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, CA, USA.
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Cui
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Ping
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China.|Key Laboratory of Tumor Immunology and Pathology of Ministry of Education, Southwest Hospital, Third Military Medical University, Chongqing, China.|Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiu-Wu
authors.initials: XW
authors.lastname: Bian
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000401:mortality / Q000473:pathology; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D020904:Glia Maturation Factor / Q000032:analysis / Q000502:physiology*; D005910:Glioma / Q000098:blood supply* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D020904:Glia Maturation Factor; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: glia maturation factor-β; glioma; neovascularization; prognosis