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 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 anti-tumor 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 TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancermore »
- Authors:
-
- North Shore Research Inst., Evanston, IL (United States). Dept. of Medicine
- Thomas Jefferson Univ., Philadelphia, PA (United States). Kimmel Cancer Center
- National Inst. for Food and Drug Control, Beijing (China)
- North Shore Research Inst., Evanston, IL (United States). Dept. of Pathology
- North Shore Research Inst., Evanston, IL (United States). Dept. of Radiology
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Northwestern Univ., Chicago, IL (United States). Dept. of Cell and Molecular Biology
- North Shore Univ. Health Sytem, Evanston, IL (United States). Dept. of Medicine
- North Shore Univ. Health Sytem, Evanston, IL (United States). Dept. of Surgery
- Publication Date:
- Research Org.:
- Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
- OSTI Identifier:
- 1224489
- Grant/Contract Number:
- AC02-06CH11357; R01CA12738; RO1CA39481
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Gene Therapy
- Additional Journal Information:
- Journal Volume: 22; Journal Issue: 3; Journal ID: ISSN 0969-7128
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Oncolytic adenovirus; prostate cancer bone metastases; decorin
Citation Formats
Xu, Weidong, Neill, Thomas, Yang, Yuefeng, Hu, Zebin, Cleveland, Elyse, Wu, Ying, Hutten, Ryan, Xiao, Xianghui, Stock, Stuart R., Shevrin, Daniel, Kaul, Karen, Brendler, Charles, Iozzo, Renato V., and Seth, Prem. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer. United States: N. p., 2014.
Web. doi:10.1038/gt.2014.110.
Xu, Weidong, Neill, Thomas, Yang, Yuefeng, Hu, Zebin, Cleveland, Elyse, Wu, Ying, Hutten, Ryan, Xiao, Xianghui, Stock, Stuart R., Shevrin, Daniel, Kaul, Karen, Brendler, Charles, Iozzo, Renato V., & Seth, Prem. The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer. United States. https://doi.org/10.1038/gt.2014.110
Xu, Weidong, Neill, Thomas, Yang, Yuefeng, Hu, Zebin, Cleveland, Elyse, Wu, Ying, Hutten, Ryan, Xiao, Xianghui, Stock, Stuart R., Shevrin, Daniel, Kaul, Karen, Brendler, Charles, Iozzo, Renato V., and Seth, Prem. Thu .
"The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer". United States. https://doi.org/10.1038/gt.2014.110. https://www.osti.gov/servlets/purl/1224489.
@article{osti_1224489,
title = {The systemic delivery of an oncolytic adenovirus expressing decorin inhibits bone metastasis in a mouse model of human prostate cancer},
author = {Xu, Weidong and Neill, Thomas and Yang, Yuefeng and Hu, Zebin and Cleveland, Elyse and Wu, Ying and Hutten, Ryan and Xiao, Xianghui and Stock, Stuart R. and Shevrin, Daniel and Kaul, Karen and Brendler, Charles and Iozzo, Renato V. and Seth, Prem},
abstractNote = {In an effort to develop a new therapy for prostate cancer 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 anti-tumor 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 TRACP 5b levels, osteocalcin levels, hypercalcemia, inhibition of cancer cachexia, and an increase in the animal survival. Finally, based on these studies, we believe that Ad.dcn can be developed as a potential new therapy for prostate cancer bone metastasis.},
doi = {10.1038/gt.2014.110},
journal = {Gene Therapy},
number = 3,
volume = 22,
place = {United States},
year = {Thu Dec 11 00:00:00 EST 2014},
month = {Thu Dec 11 00:00:00 EST 2014}
}
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