Research Paper Volume 12, Issue 13 pp 13354—13364

IL-22 promotes tumor growth of breast cancer cells in mice

Ying Zhang1, *, , Cong Liu2,3, *, , Jun Gao2,3, *, , Siqi Shao4, , Yingying Cui1, , Songlou Yin4, , Bin Pan2,3, ,

  • 1 Department of Pathology, Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University, Xuzhou 221004, China
  • 2 Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221002, China
  • 3 Blood Diseases Institute, Xuzhou Medical University, Xuzhou 221002, China
  • 4 Department of Rheumatology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University, Xuzhou 221002, China
* Equal contribution

Received: February 5, 2020       Accepted: May 25, 2020       Published: July 10, 2020
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Increased interleukin-22 (IL-22) level was reported to associate with progression of breast cancer. Regulation of IL-22 in breast cancer still needs to be elucidated. We assessed the effect of giving IL-22 in tumor growth of mice inoculated with 4T1, MCF7 and MDA-MB-231 breast cancer cells. IL-22-producing cells were analyzed in tumor tissues. We also analyzed the impact of giving IL-1β and IL-23 on IL-22 levels in tumor tissues. Giving exogenous IL-22 increased tumor size and intra-tumor Ki-67-positive cells in vivo. IL-22 increased phosphorylated STAT3 level and proliferation of breast cancer cells in vitro, an effect blocked by a STAT3-inhibitor stattic. Endogenous IL-22 mRNA level was up-regulated in tumor tissue, compared with normal mammary tissue. Innate lymphoid cell group 3 (ILC3) is a major producer of IL-22 in 4T1 tumor. Giving IL-1β and/or IL-23 increased cell proliferation in 4T1 tumor, which was reversed by concurrent use of an IL-22 neutralization antibody. IL-1β and IL-23 increased levels of IL-22 mRNA and IL-22-producing ILC3 in 4T1 tumor. Our findings suggest a mechanism for how IL-22 regulates tumor growth in breast cancer, and indicate blocking IL-22 function might reduce IL-1β- and IL-23-induced tumor progression of breast cancer.


EGF: epidermal growth factor; IL-22: interleukin-22; ILC3: innate lymphoid cell group 3; STAT3: signal transducer and activator of transcription 3; VEGF: vascular endothelial growth factor.