title: Intratumoral decorin gene delivery by AAV vector inhibits brain glioblastomas and prolongs survival of animals by inducing cell differentiation.
abstract: Glioblastoma multiforme (GBM) is the most malignant cancer in the central nervous system with poor clinical prognosis. In this study, we investigated the therapeutic effect of an anti-cancer protein, decorin, by delivering it into a xenograft U87MG glioma tumor in the brain of nude mice through an adeno-associated viral (AAV2) gene delivery system. Decorin expression from the AAV vector in vitro inhibited cultured U87MG cell growth by induction of cell differentiation. Intracranial injection of AAV-decorin vector to the glioma-bearing nude mice in vivo significantly suppressed brain tumor growth and prolonged survival when compared to control non-treated mice bearing the same U87MG tumors. Proteomics analysis on protein expression profiles in the U87MG glioma cells after AAV-mediated decorin gene transfer revealed up- and down-regulation of important proteins. Differentially expressed proteins between control and AAV-decorin-transduced cells were identified through MALDI-TOF MS and database mining. We found that a number of important proteins that are involved in apoptosis, transcription, chemotherapy resistance, mitosis, and fatty acid metabolism have been altered as a result of decorin overexpression. These findings offer valuable insight into the mechanisms of the anti-glioblastoma effects of decorin. In addition, AAV-mediated decorin gene delivery warrants further investigation as a potential therapeutic approach for brain tumors.
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. uf004693@mail2000.com.tw.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Ma
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. hondy2195@yahoo.com.tw.
authors.forename: Dueng-Yuan
authors.initials: DY
authors.lastname: Hueng
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 11490, Taiwan. haoai@ndmctsgh.edu.tw.
authors.forename: Hao-Ai
authors.initials: HA
authors.lastname: Shui
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. d49519001@ym.edu.tw.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Han
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. ssfwang@yahoo.com.tw.
authors.forename: Chi-Hsien
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan. d49405004@gmail.com.
authors.forename: Ying-Hsiu
authors.initials: YH
authors.lastname: Lai
authors.affiliation: Department of Neurology, Northwestern Brain Tumor Institute. The Robert H. Lurie Comprehensive Cancer Center, Center of Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. shiyuan.cheng@northwestern.edu.
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Cheng
authors.affiliation: Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. xxiao@email.unc.edu.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xiao
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan. mtchen@vghtpe.gov.tw.
authors.forename: Ming-Teh
authors.initials: MT
authors.lastname: Chen
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan. molly0103@gmail.com.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D058575:Decorin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000229:Dependovirus / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008819:Mice, Nude; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016019:Survival Analysis; D014161:Transduction, Genetic; D047368:Tumor Burden / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D058575:Decorin; D020543:Proteome