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

Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan 70428, Taiwan.
The Journal of Immunology (Impact Factor: 5.36). 02/2012; 188(4):1981-91. DOI: 10.4049/jimmunol.1102843
Source: PubMed

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.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The cohesin complex has essential roles in cell division, DNA damage repair and gene transcription. The transcriptional function of cohesin is thought to derive from its ability to connect distant regulatory elements with gene promoters. Genome-wide binding of cohesin in breast cancer cells frequently coincides with estrogen receptor alpha (ER), leading to the hypothesis that cohesin facilitates estrogen-dependent gene transcription. We found that cohesin modulates the expression of only a subset of genes in the ER transcription program, either activating or repressing transcription depending on the gene target. Estrogen-responsive genes most significantly influenced by cohesin were enriched in pathways associated with breast cancer progression such as PI3K and ErbB1. In MCF7 breast cancer cells, cohesin depletion enhanced transcription of TFF1 and TFF2, and was associated with increased ER binding and increased interaction between TFF1 and its distal enhancer situated within TMPRSS3. In contrast, cohesin depletion reduced c-MYC mRNA and was accompanied by reduced interaction between a distal enhancer of c-MYC and its promoters. Our data indicates that cohesin is not a universal facilitator of ER-induced transcription and can even restrict enhancer-promoter communication. We propose that cohesin modulates transcription of estrogen-dependent genes to achieve appropriate directionality and amplitude of expression. Copyright © 2014. Published by Elsevier B.V.
    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 12/2014; 1849(3). DOI:10.1016/j.bbagrm.2014.12.011 · 5.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Purpose: To study the kinetics of gene expression alterations following radiation exposure of isogenic HCT116 p53 +/+ and HCT116 p53 -/- cell lines. Materials and methods: Cells were exposed to 5 Grey (Gy) of irradiation (Cs-137) and genome-wide temporal expression analysis using Illumina bead chip arrays was performed. Signalling pathways were explored using Metacore (Genego). Biological responses including cell cycle checkpoint activation, centrosome amplification and senescence induction were analysed. Results: Significant differences in the radiation response were observed between the p53 +/+ and the p53 -/- cell lines. In p53 +/+ cells concurrent G1- and G2-arrests were activated followed by senescence induction. Increased expression of genes associated with senescence, senescence secretory phenotype (SASP) and repression of genes essential for G2-M transition were detected. P53 -/- cells arrested mainly in G2 followed by centrosome amplification, mitotic slippage and a subsequent increase of polyploid cells. Furthermore, changes in expression correlated well with these signs of mitotic catastrophe. Conclusions: The presence or absence of p53 triggers different signalling cascades with different endpoints. Elucidating these differences is important as it enables improvement of radiation treatment and could be used to develop new combination treatments with specific inhibitors of key regulators of these cell death modalities.
    International Journal of Radiation Biology 09/2014; 91(1):1-30. DOI:10.3109/09553002.2015.959668 · 1.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Metastases to the spine is a common manifestation of breast cancer leading to considerable reduction in the patient's quality of life. Physicians must consider the different treatments available to decrease pain, reduce tumor burden, and ensure spinal stability in order to prevent neurologic compromises. The objective of this study is to analyze the epidemiology and outcomes of patients with spinal metastases from breast cancer and describe changes over time in these lesions. Second objective is to establish the current treatment of spinal metastases in this cancer.
    World Neurosurgery 08/2014; 82(6). DOI:10.1016/j.wneu.2014.08.010 · 2.42 Impact Factor

Full-text (2 Sources)

Available from
May 31, 2014