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Open Access Highly Accessed Research article

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

Runqiu Jiang12, Haiyang Wang23, Lei Deng12, Jiajie Hou12, Ruihua Shi3, Ming Yao12, Yun Gao12, Aihua Yao12, Xuehao Wang12, Lianzhen Yu3* and Beicheng Sun12*

Author Affiliations

1 Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, P.R. China

2 The key Laboratory of living donor liver transplantation, Ministry of Health, Nanjing, P.R. China

3 Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, P.R. China

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BMC Cancer 2013, 13:59  doi:10.1186/1471-2407-13-59

Published: 5 February 2013

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.

Keywords:
Colon cancer; Ulcerative colitis; IL-22; TILs; STAT3