title: IL-33 Promotes Gastric Cancer Cell Invasion and Migration Via ST2-ERK1/2 Pathway.
abstract: BACKGROUND
  As a pro-inflammatory cytokine, IL-33 has been demonstrated to play an important role in tumor progression. It is reported that IL-33 is highly expressed in the serum and tumor tissues of patients with gastric cancer. However, the function of IL-33 in gastric cancer remains elusive. We here tried to elucidate the effects of IL-33 on gastric cancer cell invasion and migration.
  
  
  METHODS
  Invasion assay and migration assay were performed to assess the effects of IL-33 on gastric cancer cell invasion and migration. ST2 receptor was silenced by siRNA, and ERK1/2 pathway was inhibited by U0126. Protein levels of MMP-3 and IL-6 in cell supernatant were measured by ELISA.
  
  
  RESULTS
  IL-33 promoted the invasion and migration of gastric cancer cells, in a dose-dependent manner. Knockdown of the IL-33 receptor ST2 attenuated the IL-33-mediated invasion and migration. Furthermore, via ST2 receptor, IL-33 induced the activation of ERK1/2 and increased the secretion of MMP-3 and IL-6. In addition, blockage of ERK1/2 pathway resulted in inhibition of invasion and migration induced by IL-33, and downregulation of MMP-3 and IL-6 production.
  
  
  CONCLUSIONS
  IL-33 promotes gastric cancer cell invasion and migration by stimulating the secretion of MMP-3 and IL-6 via ST2-ERK1/2 pathway. Thus, IL-33 may be a useful marker for the diagnosis and treatment of gastric cancer.
authors: Department of Interventional Radiology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China, xxiangyu1@163.com.
authors: Xi-Xiang
authors: XX
authors: Yu
authors: Zhe
authors: Z
authors: Hu
authors: Xian
authors: X
authors: Shen
authors: Li-Yang
authors: LY
authors: Dong
authors: Wei-Zhong
authors: WZ
authors: Zhou
authors: Wen-Hao
authors: WH
authors: Hu
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013997:Time Factors; D014162:Transfection
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; C508600:IL6 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D015850:Interleukin-6; D007378:Interleukins; D047428:Protein Kinase Inhibitors; D011956:Receptors, Cell Surface; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3
references: Asian Pac J Cancer Prev. 2014;15(8):3503-5
references: 24870747
references: Biochim Biophys Acta. 1991 Aug 27;1090(1):1-8
references: 1832015
references: J Immunol. 2010 Nov 15;185(10 ):5743-50
references: 20926795
references: Oncoimmunology. 2012 Mar 1;1(2):229-231
references: 22720252
references: Transl Oncol. 2013 Jun 01;6(3):311-8
references: 23730411
references: Cell Biol Int. 2014 May;38(5):655-62
references: 24448827
references: J Immunol. 2012 Jul 1;189(1):403-10
references: 22634619
references: J Pathol. 2013 Oct;231(2):180-9
references: 23775566
references: BMC Cancer. 2014 Mar 18;14 :198
references: 24636276
references: Hum Reprod. 2013 Aug;28(8):2126-33
references: 23739220
references: Oncogene. 2007 May 14;26(22):3279-90
references: 17496922
references: Clin Exp Allergy. 2014 Apr;44(4):540-52
references: 24479526
references: Immunity. 2005 Nov;23 (5):479-90
references: 16286016
references: Dig Dis Sci. 2011 Dec;56(12):3596-601
references: 21643739
references: Int J Mol Med. 2012 Apr;29(4):530-40
references: 22246057
references: Rev Esp Enferm Dig. 2012 Mar;104(3):134-41
references: 22449155
references: Neuroscience. 2013 Dec 3;253:172-82
references: 23988433
references: J Cereb Blood Flow Metab. 1999 Nov;19(11):1279-88
references: 10566975
references: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references: 21296855
references: Int J Cancer. 2014 Apr 1;134(7):1669-82
references: 24105680
references: J Int Med Res. 2012;40(5):1654-61
references: 23206447
references: Asian Pac J Cancer Prev. 2013;14(4):2563-6
references: 23725175
references: Front Immunol. 2014 Apr 07;5:141
references: 24778632
references: Asian Pac J Cancer Prev. 2013;14(12):7763
references: 24460366
references: Gastric Cancer. 2009;12(2):95-100
references: 19562463
references: EMBO J. 1994 Mar 1;13(5):1176-88
references: 8131748
references: Br J Haematol. 2013 Mar;160(5):709-10
references: 23205532