title: The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer.
abstract: In an effort to develop a new therapy for prostate cancer (PCa) bone metastases, we have created Ad.dcn, a recombinant oncolytic adenovirus carrying the human decorin gene. Infection of PC-3 and DU-145, the human prostate tumor cells, with Ad.dcn or a non-replicating adenovirus Ad(E1-).dcn resulted in decorin expression; Ad.dcn produced high viral titers and cytotoxicity in human prostate tumor cells. Adenoviral-mediated decorin expression inhibited Met, the Wnt/β-catenin signaling axis, vascular endothelial growth factor A, reduced mitochondrial DNA levels and inhibited tumor cell migration. To examine the antitumor response of Ad.dcn, PC-3-luc cells were inoculated in the left heart ventricle to establish bone metastases in nude mice. Ad.dcn, in conjunction with control replicating and non-replicating vectors were injected via tail vein. The real-time monitoring of mice, once a week, by bioluminescence imaging and X-ray radiography showed that Ad.dcn produced significant inhibition of skeletal metastases. Analyses of the mice at the terminal time point indicated a significant reduction in the tumor burden, osteoclast number, serum tartrate-resistant acid phosphatase 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia and an increase in the animal survival. Based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for PCa bone metastasis.
authors.affiliation: Gene Therapy Program, Department of Medicine, NorthShore Research Institute, an affiliate of the University of Chicago, Evanston, IL, USA.
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pathology, Anatomy and Cell Biology and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Neill
authors.affiliation: Gene Therapy Program, Department of Medicine, NorthShore Research Institute, an affiliate of the University of Chicago, Evanston, IL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1st Division of in Vitro Diagnostic Reagents, National Institutes for Food and Drug Control, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Pathology, NorthShore Research Institute, Evanston, IL, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cleveland
authors.affiliation: Image processing Lab, Department of Radiology, NorthShore Research Institute, Evanston, IL, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Image processing Lab, Department of Radiology, NorthShore Research Institute, Evanston, IL, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hutten
authors.affiliation: Advanced Photon Source, Argonne National Lab, Lemont, IL, USA.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Cell and Molecular Biology, Northwestern University, Chicago, IL, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Stock
authors.affiliation: Department of Medicine, NorthShore Research Institute, Evanston, USA.
authors.forename: D
authors.initials: D
authors.lastname: Shevrin
authors.affiliation: Department of Pathology, NorthShore Research Institute, Evanston, IL, USA.
authors.forename: K
authors.initials: K
authors.lastname: Kaul
authors.affiliation: Department of Surgery, NorthShore University HealthSytem, Evanston, IL, USA.
authors.forename: C
authors.initials: C
authors.lastname: Brendler
authors.affiliation: Department of Pathology, Anatomy and Cell Biology and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: R V
authors.initials: RV
authors.lastname: Iozzo
authors.affiliation: Gene Therapy Program, Department of Medicine, NorthShore Research Institute, an affiliate of the University of Chicago, Evanston, IL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Seth
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary* / Q000628:therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D058575:Decorin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000628:therapy*
chemical_list: D058575:Decorin