IMR Press / EJGO / Volume 41 / Issue 2 / DOI: 10.31083/j.ejgo.2020.02.4970
Open Access Original Research
Interleukin-22 derived from cervical cancer-associated fibroblasts accelerates senescence of normal fibroblasts and promotes expression of tumorigenesis-related factors in HeLa cells
L. Xu1,2H. Cai2,*N. Zhu3Bo Zheng1
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1 Department of Obstetrics and Gynecology, Central Hospital, Xianning, China
2 Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Hubei Cancer Clinical Study, Hubei Key Laboratory of Tumor Biological Behaviors, 430071 Wuhan, China
3 Department of Medical Microbiology, School of Basic Medicine Sciences, Hubei University of Science and Technology, Xianning, China
Eur. J. Gynaecol. Oncol. 2020, 41(2), 192–199;
Published: 15 April 2020

The present study aimed to evaluate the effect of interleukin-22 (IL-22), secreted by cervical cancer-associated fibroblasts (CAFs), on the senescence of normal fibroblasts (NFs) and the malignant characteristics of cancer cells. CAFs and NFs were isolated from clinical tissue samples and the degrees of senescence were compared. NFs were cultured with a CAF-conditioned medium and analyzed for the expression of senescence markers. HeLa cells were cultured with an exogenous IL-22 supplement and analyzed for the expression of tumor markers. Compared to NFs, CAFs showed a delayed growth and an elevated activity of senescence-associated β-galactosidase (SA β-gal). Expression of α-SMA, p16, and IL-22 was upregulated in the CAFs. Further, the CAF-conditioned medium promoted the senescence of NFs through the suppression of cell proliferation and the elevated expression of α-SMA and p16; whereas the addition of an IL-22 antibody reversed the senescence process. Exogenous IL-22 upregulated N-cadherin and downregulated E-cadherin in HeLa cells. The IL-22 supplement also increased the expression of VEGF, MMP2, and MMP9 in HeLa cells. In conclusion, IL-22 produced by CAFs accelerated the senescence of NFs and promoted the expression of tumorigenesis-related factors in HeLa cells.

Cervical cancer
Cancer-associated fibroblasts
Figure 1.
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