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  • Title: Upregulated IL-19 in breast cancer promotes tumor progression and affects clinical outcome.
    Author: Hsing CH, Cheng HC, Hsu YH, Chan CH, Yeh CH, Li CF, Chang MS.
    Journal: Clin Cancer Res; 2012 Feb 01; 18(3):713-25. PubMed ID: 22186257.
    Abstract:
    PURPOSE: Interleukin (IL)-19 was expressed in invasive ductal carcinoma (IDC) of the breast tissue but not in healthy breast tissue. We explored the effects of IL-19 on the pathogenesis of breast cancer and its clinical outcome. EXPERIMENTAL DESIGN: Tumor expression of IL-19 was assessed by immunohistochemistry and/or real-time quantitative PCR between two groups of patients with breast IDC (n = 60 and 143, respectively) with available clinical and survival data. We examined the effects of IL-19 on cytokine and chemokine production as well as proliferation and migration in breast cancer cells. Mice were injected with IL-19-overexpressing or vector control 67NR cells and the tumor growth and lung metastatic micronodules were measured. RESULTS: Of the IDC specimens, high IL-19 expression was associated with advanced tumor stage, high tumor metastasis, and worse survival. In vitro, IL-19 induced transcripts of IL-1β, IL-6, TGF-β, matrix metalloproteinase (MMP)2, MMP9, and CXCR4 in 4T1 breast cancer cells; induced fibronectin expression and assembly; and promoted cancer cell proliferation and migration, which were inhibited by anti-IL-19 monoclonal antibody (mAb). Endogenous fibronectin expression and cancer cell migration were lower in IL-19 knockdown 4T1 cells. In 4T1 cells, hypoxia induced IL-19 and CXCR4 expression, which was inhibited by anti-IL-19 mAb. IL-19 overexpression in noninvasive 67NR cancer cells increased cell proliferation and migration. In vivo, mice injected with IL-19-overexpressing 67NR cell clones showed larger tumors and more metastatic micronodules in the lung. CONCLUSIONS: High IL-19 expression in breast cancer tissue is associated with a poor clinical outcome. IL-19 is pivotal in the pathogenesis of breast cancer.
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