title: IL-33/ST2 pathway contributes to metastasis of human colorectal cancer.
abstract: 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.
authors.affiliation: Department of Oncology, The People's Hospital of Linyi Economic and Technological Development Zone, Linyi 276000, China.
authors.forename: Xuejian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Radiotherapy, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Radiotherapy, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Radiotherapy, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Bian
authors.affiliation: Department of Oncology, The People's Hospital of Linyi Economic and Technological Development Zone, Linyi 276000, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Oncology, The People's Hospital of Linyi Economic and Technological Development Zone, Linyi 276000, China.
authors.forename: Wenchuan
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Radiotherapy, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. Electronic address: qlqintj@126.com.
authors.forename: Qingliang
authors.initials: Q
authors.lastname: Qin
mesh_terms: D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: C527276:CXCR4 protein, human; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015850:Interleukin-6; D007378:Interleukins; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Colorectal cancer; IL-33; ST2; Tumor metastasis