IL-33/ST2 pathway contributes to metastasis of human colorectal

Interleukin-33 (IL-33) was recently implicated in cancer pathogenesis. However, the possible effect of IL-33 on tumor progression of colorectal cancer (CRC), which is one of the most commonly diagnosed and lethal cancers worldwide, was still unclear. Here we evaluated the potential role of 1L-33/ST2 pathway in metastasis of human CRC. We found an elevated expression of IL-33 and ST2 in tumor tissues of CRC patients. Higher expressions of IL-33 and ST2 were observed in poor-differentiated human CRC cells. Of note, IL-33 stimulation promoted the invasion of human CRC cells in a dose dependent manner. Enhanced IL-33/ST2 signaling promoted CRC metastasis, while attenuated IL-33/ST2 signaling decreased CRC metastasis. In consistent, enforced IL-33 expression in human CRC cells enhanced their growth, metastasis and reduced the survival time in nude mice, while decreased IL-33 expression in human CRC cells inhibited their growth, metastasis and prolonged the survival time in nude mice. Finally, we observed an increased expression of IL-6, CXCR4, MMP2 and MMP9 in response to IL-33/ST2 signaling in human CRC cells, which were crucial for the enhanced metastasis by IL-33 stimulation. Collectively, our findings demonstrated that IL-33/ST2 pathway could contribute to the metastasis of human CRC, which could enlarge the understanding of CRC pathogenesis and provide clues for developing new CRC therapeutics. (C) 2014 Elsevier Inc. All rights reserved.