Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways
Epidermal growth factor receptor (EGFR) and androgen receptor (AR) pathways play pivotal roles in prostate cancer progression. Therefore, agents with dual-targeting ability may have important therapeutic potential. Decorin, a proteoglycan present in the tumor microenvironment, is known to regulate m...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-10-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558609800079 |
| _version_ | 1828937896790327296 |
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| author | Yunping Hu Haiguo Sun Rick T. Owens Jiansheng Wu Yong Q. Chen Isabelle M. Berquin Donna Perry Joseph T. O'Flaherty Iris J. Edwards |
| author_facet | Yunping Hu Haiguo Sun Rick T. Owens Jiansheng Wu Yong Q. Chen Isabelle M. Berquin Donna Perry Joseph T. O'Flaherty Iris J. Edwards |
| author_sort | Yunping Hu |
| collection | DOAJ |
| description | Epidermal growth factor receptor (EGFR) and androgen receptor (AR) pathways play pivotal roles in prostate cancer progression. Therefore, agents with dual-targeting ability may have important therapeutic potential. Decorin, a proteoglycan present in the tumor microenvironment, is known to regulate matrix assembly, growth factor binding, and receptor tyrosine kinase activity. Here, we show that in prostate-specific PtenP-/- mice, a genetically defined, immune-competent mouse model of prostate cancer, systemic delivery of decorin inhibits tumor progression by targeting cell proliferation and survival pathways. Moreover, in human prostate cancer cells, we show that decorin specifically inhibits EGFR and AR phosphorylation and cross talk between these pathways. This prevents AR nuclear translocation and inhibits the production of prostate specific antigen. Further, the phosphatidylinositol-3 kinase (PI3K)/Akt cell survival pathway is suppressed leading to tumor cell apoptosis. Those findings highlight the effectiveness of decorin in the presence of a powerful genetic cancer risk and implicate decorin as a potential new agent for prostate cancer therapy by targeting EGFR/AR-PI3K-Akt pathways. |
| first_indexed | 2024-12-14T02:33:26Z |
| format | Article |
| id | doaj.art-ef65541785d046ef8f907e8c77f76205 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-14T02:33:26Z |
| publishDate | 2009-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-ef65541785d046ef8f907e8c77f762052022-12-21T23:20:12ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022009-10-0111101042105310.1593/neo.09760Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor PathwaysYunping Hu0Haiguo Sun1Rick T. Owens2Jiansheng Wu3Yong Q. Chen4Isabelle M. Berquin5Donna Perry6Joseph T. O'Flaherty7Iris J. Edwards8Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USALifeCell Corporation, One Millennium, Branchburg, NJ 08876, USADepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USALifeCell Corporation, One Millennium, Branchburg, NJ 08876, USADepartment of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USAEpidermal growth factor receptor (EGFR) and androgen receptor (AR) pathways play pivotal roles in prostate cancer progression. Therefore, agents with dual-targeting ability may have important therapeutic potential. Decorin, a proteoglycan present in the tumor microenvironment, is known to regulate matrix assembly, growth factor binding, and receptor tyrosine kinase activity. Here, we show that in prostate-specific PtenP-/- mice, a genetically defined, immune-competent mouse model of prostate cancer, systemic delivery of decorin inhibits tumor progression by targeting cell proliferation and survival pathways. Moreover, in human prostate cancer cells, we show that decorin specifically inhibits EGFR and AR phosphorylation and cross talk between these pathways. This prevents AR nuclear translocation and inhibits the production of prostate specific antigen. Further, the phosphatidylinositol-3 kinase (PI3K)/Akt cell survival pathway is suppressed leading to tumor cell apoptosis. Those findings highlight the effectiveness of decorin in the presence of a powerful genetic cancer risk and implicate decorin as a potential new agent for prostate cancer therapy by targeting EGFR/AR-PI3K-Akt pathways.http://www.sciencedirect.com/science/article/pii/S1476558609800079 |
| spellingShingle | Yunping Hu Haiguo Sun Rick T. Owens Jiansheng Wu Yong Q. Chen Isabelle M. Berquin Donna Perry Joseph T. O'Flaherty Iris J. Edwards Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways Neoplasia: An International Journal for Oncology Research |
| title | Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways |
| title_full | Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways |
| title_fullStr | Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways |
| title_full_unstemmed | Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways |
| title_short | Decorin Suppresses Prostate Tumor Growth through Inhibition of Epidermal Growth Factor and Androgen Receptor Pathways |
| title_sort | decorin suppresses prostate tumor growth through inhibition of epidermal growth factor and androgen receptor pathways |
| url | http://www.sciencedirect.com/science/article/pii/S1476558609800079 |
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