Anti-IL-20 Monoclonal Antibody Suppresses Prostate Cancer Growth and Bone Osteolysis in Murine Models

• Published in: PloS one 2015-10, Vol.10 (10), p.e0139871-e0139871
• Main Authors: Hsu, Yu-Hsiang, Wu, Cheng-Ying, Hsing, Chung-Hsi, Lai, Wei-Ting, Wu, Li-Wha, Chang, Ming-Shi
• Format: Article
• Language: English
• Subjects: AKT protein; Analysis; Anesthesiology; Animal models; Animals; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Biochemistry; Biocompatibility; Biomedical materials; Bladder; Bone cancer; Bone density; Bone growth; Bone mineral density; Breast cancer; Cadherins; Cancer; Cathepsin G; Cathepsin K; Cell adhesion & migration; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Colonies; Cytokines; Disease Models, Animal; Drug therapy; Fibronectin; Gene expression; Genetic aspects; Growth; Growth factors; Humans; Inflammation; Interleukin 20; Interleukins; Interleukins - immunology; Kinases; Male; Medicine; Metastasis; Mice; Molecular biology; Monoclonal antibodies; N-Cadherin; NF-κB protein; Osteolysis; Osteolysis - drug therapy; Osteolysis - immunology; Osteolysis - pathology; Pathogenesis; Physiological aspects; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - immunology; Prostatic Neoplasms - pathology; Protein expression; Receptors; Receptors, Interleukin - metabolism; Signal Transduction; Tumor cell lines; Tumors; Up-Regulation - drug effects; Xenografts; Xenotransplantation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139871

Interleukin (IL)-20 is a proinflammatory cytokine in the IL-10 family. IL-20 is associated with tumor promotion in the pathogenesis of oral, bladder, and breast cancer. However, little is known about the role of IL-20 in prostate cancer. We hypothesize that IL-20 promotes the growth of prostate cancer cells. Immunohistochemical staining showed that IL-20 and its receptors were expressed in human PC-3 and LNCaP prostate cancer cell lines and in prostate tumor tissue from 40 patients. In vitro, IL-20 upregulated N-cadherin, STAT3, vimentin, fibronectin, RANKL, cathepsin G, and cathepsin K, and increased the migration and colony formation of prostate cancer cells via activated p38, ERK1/2, AKT, and NF-κB signals in PC-3 cells. We investigated the effects of anti-IL-20 monoclonal antibody 7E on prostate tumor growth in vivo using SCID mouse subcutaneous and intratibial xenograft tumor models. In vivo, 7E reduced tumor growth, suppressed tumor-mediated osteolysis, and protected bone mineral density after intratibial injection of prostate cancer cells. We conclude that IL-20 is involved in the cell migration, colony formation, and tumor-induced osteolysis of prostate cancer. Therefore, IL-20 might be a novel target for treating prostate cancer.