title: Heat Shock Protein 47 Promotes Glioma Angiogenesis.
abstract: Heat shock protein 47 (HSP47) is a collagen-binding protein, which has been recently found to express in glioma vessels. However, the expression profile of HSP47 in glioma patients and the underlying mechanisms of HSP47 on glioma angiogenesis are not fully explored. In the current study, we found that expression of HSP47 in glioma vessels was correlated with the grades of gliomas. HSP47 knockdown by siRNAs significantly decreased cell viability in vitro and tumor volume in vivo; moreover, it reduced the microvessel density (MVD) by CD31 immunohistochemistry in vivo. HSP47 knockdown significantly inhibited tube formation, invasion and proliferation of human umbilical vein endothelial cells (HUVECs). Furthermore, conditional medium derived from HSP47 knockdown cells significantly inhibited HUVECs tube formation and migration, while it increased chemosensitivity of HUVECs cells to Avastin. Silencing of HSP47 decreased VEGF expression in glioma cells consistently, and reduced glioma vasculature. Furthermore, HSP47 promoted glioma angiogenesis through HIF1α-VEGFR2 signaling. The present study demonstrates that HSP47 promotes glioma angiogenesis and highlights the importance of HSP47 as an attractive therapeutic target of GBM.
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhe Bao
authors.initials: ZB
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Shao Jian
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhi Gen
authors.initials: ZG
authors.lastname: Leng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Yu Hang
authors.initials: YH
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wen Lei
authors.initials: WL
authors.lastname: Yang
authors.affiliation: Department of Immunology and Biotherapy Research Center, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Yi Wei
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX.
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei Guo
authors.initials: WG
authors.lastname: Zhao
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000473:pathology*; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics
chemical_list: D050958:HSP47 Heat-Shock Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D048052:Mitogen-Activated Protein Kinase 3; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; C497442:HIF1A protein, human; C494660:SERPINH1 protein, human; C508053:ERBB2 protein, human; C000588866:KDR protein, human
keywords: VEGFR2; angiogenesis; glioblastoma; glioma; heat shock protein 47