title: HSP47 Promotes Glioblastoma Stemlike Cell Survival by Modulating Tumor Microenvironment Extracellular Matrix through TGF-β Pathway.
abstract: Grade IV glioblastoma multiforme (GBM) is the most malignant form of gliomas. HSP47, encoded by SERPINH1 gene, is a serpin which serves as a human chaperone protein for collagen. We have shown that HSP47 is significantly overexpressed in GBM and associated with tumor grade. However, the role of HSP47 on GBM progression and stemlike property remains unclear. The stable overexpression of HSP47 in primary GBM cells was established by lentivirus infection. The effects of HSP47 overexpression on tumor growth and the effects of blocking the TGF-β pathway on tumor regression were investigated by animal study. The expression of HSP47 was examined by real time qRT-PCR and immunohistochemistry. The stemlike property was investigated by sphere formation and CD44 cell population analysis using flow cytometry. We found that overexpression of HSP47 promotes primary glioma cell tumor formation, invasion, angiogenesis, and stemlike properties. The overexpression of HSP47 was correlated and promoted extracellular matrix (ECM) related genes through the TGF-β pathway in GBM. Blocking TGF-β pathway overcomes HSP47 induced tumorigenesis and stemness. This study demonstrated that HSP47 promotes GBM stemlike cell survival by modulating tumor microenvironment ECM through TGF-β pathway. Blocking the TGF-β pathway provides a promising therapeutic potential for HSP47 overexpressed GBM.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Jiang
authors.forename: Taofeng
authors.initials: T
authors.lastname: Zhou
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, First Hospital of Jilin University , Changchun, Jilin 130021, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Qi
authors.affiliation: Department of Pathology, Sir Run Run Hospital & Nanjing Medical University , Nanjing 211166, China.
authors.forename: Hongping
authors.initials: H
authors.lastname: Xia
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D050958:HSP47 Heat-Shock Proteins; C530108:LY2109761; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011720:Pyrazoles; D011758:Pyrroles; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta
keywords: Glioblastoma; HSP47; TGF-β; extracellular matrix; glioma stem cell; inhibitor