IL-22 is related to development of human colon cancer by activation of STAT3

BMC Cancer. 2013 Feb 5;13:59. doi: 10.1186/1471-2407-13-59.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antigens, CD / analysis
  • Apoptosis / physiology
  • Blotting, Western
  • Colitis, Ulcerative / metabolism*
  • Colonic Neoplasms / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukins / metabolism*
  • Lymph Nodes / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Proteins
  • STAT3 Transcription Factor / physiology*
  • Tumor Microenvironment / physiology
  • Up-Regulation

Substances

  • Antigens, CD
  • Interleukins
  • Neoplasm Proteins
  • STAT3 Transcription Factor
  • interleukin-22