title: IL-22 is related to development of human colon cancer by activation of STAT3.
abstract: BACKGROUND
  It has been previously reported that IL-22, one of the cytokines secreted by Th17 cells, demonstrates both a protective and inflammatory promotion effect in inflammatory bowel disease (IBD) through STAT3 signaling activation. We sought to investigate the role of IL-22 expression in colon cancer (CC).
  
  
  METHODS
  The expression of IL-22 and related molecules were detected in human CC, the detail function and mechanism of IL-22 were investigated by in vivo and in vitro model.
  
  
  RESULTS
  Our results demonstrated significant upregulation of IL-22 in human CC tumor infiltrated leukocytes (TILs) compared to peripheral lymphocytes. Moreover, our findings demonstrated that IL-22 expression was significantly higher in ulcerative colitis (UC) tissues versus normal colon tissues. Both IL-22 receptor α1 (IL-22RA1) and IL-23 were highly expressed in CC and UC tissues compared to normal controls. TILs exhibiting various IL-22 expression levels isolated from CC patients were demonstrated to enhance tumor growth and metastasis co-transplanted with Hct-116 cells underwent subcutaneous transplantation in mice model. Tumor growth and metastasis was promoted by STAT3 phosphorylation and upregulation of its downstream genes such as Bcl-xl, CyclinD1, and VEGF. In vitro studies confirmed the anti-apoptotic and pro-proliferation effect of IL-22 according to the BrdU cooperation assay and peroxide induced apoptosis analysis with or without the presence of IL-22.
  
  
  CONCLUSIONS
  In this study we demonstrated that excessive IL-22 in the CC and UC microenvironment leads to tumor growth, inhibition of apoptosis, and promotion of metastasis depend on STAT3 activation.
authors: Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, PR China.
authors: Runqiu
authors: R
authors: Jiang
authors: Haiyang
authors: H
authors: Wang
authors: Lei
authors: L
authors: Deng
authors: Jiajie
authors: J
authors: Hou
authors: Ruihua
authors: R
authors: Shi
authors: Ming
authors: M
authors: Yao
authors: Yun
authors: Y
authors: Gao
authors: Aihua
authors: A
authors: Yao
authors: Xuehao
authors: X
authors: Wang
authors: Lianzhen
authors: L
authors: Yu
authors: Beicheng
authors: B
authors: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor / Q000502:physiology*; D059016:Tumor Microenvironment / Q000502:physiology; D015854:Up-Regulation; D000097043:Interleukin-22
chemical_list: D015703:Antigens, CD; D007378:Interleukins; D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22
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