Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models (161.10)

Abstract

Abstract IL-20 is a proinflammatory cytokine involved in rheumatoid arthritis and osteoporosis. However, little is known about the role of IL-20 in breast cancer. We explored the function of IL-20 in tumor growth and metastasis, and its clinical outcome. Tumor expression of IL-20 was assessed by IHC staining among 198 breast invasive ductal carcinoma (IDC) patients with available clinical and survival data. IL-20 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. RTQ-PCR showed that clinical breast tumor tissue expressed higher IL-20 and its receptors than did non-tumorous 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 monoclonal antibody (mAb) 7E. In vivo, 7E reduced tumor growth, suppressed bone colonization, reduced 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.