title: Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models.
abstract: IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis, atherosclerosis, and stroke. However, little is known about its role in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, as well as in clinical outcome. Tumor expression of IL-20 was assessed by immunohistochemical staining among 198 patients with invasive ductal carcinoma of the breast, using available clinical and survival data. IL-20 expression was associated with advanced tumor stage, greater tumor metastasis, and worse survival. Reverse transcription quantitative polymerase chain reaction showed that clinical breast tumor tissue expressed higher levels of IL-20 and its receptors than did nontumorous breast tissue. IL-20 was also highly expressed in breast cancer bone-metastasis tissue. In vitro, IL-20 upregulated matrix metalloproteinase-9, matrix metalloproteinase-12, cathepsin K, and cathepsin G, and enhanced proliferation and migration of breast cancer cells, which were inhibited by anti-IL-20 mAb 7E. In vivo, we generated murine models to evaluate the therapeutic potential of 7E, using luminescence intensity, radiological scans, and micro-computed tomography. 7E reduced tumor growth, suppressed bone colonization, diminished tumor-mediated osteolysis, and lessened bone density decrement in mice injected with breast cancer cells. In conclusion, our results suggest that IL-20 plays pivotal roles in the tumor progression of breast cancer. IL-20 expression in breast cancer tissue is associated with a poor clinical outcome. Anti-IL-20 mAb 7E suppressed bone colonization and decreased osteolytic bone lesions. Therefore, IL-20 may be a novel target in treating breast tumor-induced osteolysis.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
authors.forename: Yu-Hsiang
authors.initials: YH
authors.lastname: Hsu
authors.forename: Chung-Hsi
authors.initials: CH
authors.lastname: Hsing
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Chan
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Chang
authors.forename: Jing-Jou
authors.initials: JJ
authors.lastname: Yan
authors.forename: Ming-Shi
authors.initials: MS
authors.lastname: Chang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D001842:Bone and Bones / Q000473:pathology; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D056649:Cathepsin G / Q000096:biosynthesis; D056657:Cathepsin K / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D005260:Female; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000276:immunology* / Q000494:pharmacology; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D010014:Osteolysis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D007378:Interleukins; D056649:Cathepsin G; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12; C422042:interleukin 20