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

Yu Hsiang Hsu, Chung-Hsi Hsing, Chien Feng Li, Chien Hui Chan, Ming Chung Chang, Jing Jou Yan, Ming Shi Chang

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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.

Original languageEnglish
Pages (from-to)1981-1991
Number of pages11
JournalJournal of Immunology
Volume188
Issue number4
DOIs
Publication statusPublished - Feb 15 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Hsu, Y. H., Hsing, C-H., Li, C. F., Chan, C. H., Chang, M. C., Yan, J. J., & Chang, M. S. (2012). Anti-IL-20 monoclonal antibody suppresses breast cancer progression and bone osteolysis in murine models. Journal of Immunology, 188(4), 1981-1991. https://doi.org/10.4049/jimmunol.1102843