Melanoma cells heterogeneously express IL-18 receptors and consis

selleck products melanoma cells heterogeneously express IL-18 receptors and consistent with its potential prometastatic action, we reported that experimental melanoma metastases are prevented in both ICE-deficient mice lacking secreted IL-18 and IL-18-binding protein-treated mice. Moreover, SYN-117 order IL-18 promotes melanoma metastasis at multiple steps, including stimulating the capillary arrest of circulating tumor cells, immune escape, angiogenesis, and tumor cell proliferation. However, at the moment, the molecular mechanisms underlying IL-18-dependent

melanoma metastasis have not been elucidated. The aim of this study was to identify molecular mediators of IL-18 by exploring the melanoma cell gene display induced by this cytokine. We compared global gene expression between untreated and IL-18-treated melanomas using a high-throughput human 36 K cDNA microarray platform. Total RNA from four primary cultured human melanoma cell Acalabrutinib manufacturer lines was used: two VLA-4-expressing highly-metastatic cell lines (A375 and 1182 melanoma), and two non-VLA-4

expressing low metastatic cell lines (526 and 624-28 melanoma). Gene profile was determined by cDNA microarray and real-time PCR. We found around 50 genes over-expressed (ANOVA, p < 0.05) in IL-18-treated highly metastatic versus low-metastatic melanoma cells. Some of these genes were also co-expressed by effect of soluble VCAM-1 on highly metastatic but not Histone demethylase on low-metastatic melanoma cells. None of these genes were expressed by melanoma patients that did not metastasize to distant

sites within 4 years after diagnosis, while majority of them were expressed in melanomas associated with high risk of metastasis and death. In summary, we identified the biological and clinical relevance of IL-18-dependent genes for highly metastatic VLA-4-expressing human melanoma, and suggest molecular pathways relevant to melanoma metastasis in the inflammatory microenvironment of IL-18. O30 Interleukin-8 Expression is Regulated by Histone Deacetylases through NF-kB Pathway in Breast Cancer Carine Chavey1, David Vindireux1, Carine Bossard1, Marcus Muehlbauer2, Christian Jorgensen1, Christian Jobin2, Gwendal Lazennec 1 1 U844, INSERM, Montpellier, France, 2 Department of Medicine, Pharmacology and Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, NC, USA We have recently reported that IL-8/CXCL8 was overexpressed in invasive estrogen receptor (ERalpha)-negative breast cancer cells, compared to ERa-positive breast cancer cells. We now demonstrate that histone deacetylases (HDAC) play an essential role in the regulation of IL-8 gene expression in ERalpha-positive MCF-7 breast cancer cells. Treatment of MCF-7 cells with the HDAC inhibitor trichostatin A (TSA) led to a strong up-regulation of IL-8 protein and RNA levels in MCF-7 cells.

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