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

• Elevated expressions of IL-33 and ST2 in tumor tissues of CRC patients.
• Higher expressions of IL-33 and ST2 in poor-differentiated human CRC cells.
• Enhanced IL-33/ST2 signaling promoted human CRC metastasis.
• Attenuated IL-33/ST2 signaling attenuated human CRC metastasis.
• IL-33/ST2 pathway modulated IL-6 and MMPs expressions in human CRC cells.

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 IL-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.