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European Journal of Gynaecological Oncology  2020, Vol. 41 Issue (2): 192-199    DOI: 10.31083/j.ejgo.2020.02.4970
Original Research Previous articles | Next articles
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, 2, H. Cai2, *(), N. Zhu3, Bo Zheng1
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
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Abstract  
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.
Key words:  Cervical cancer      Interleukin-22      Senescence      Cancer-associated fibroblasts      Oncogenesis     
Published:  15 April 2020     
Fund: 
BK1510/Research Project of Hubei University of Science and Technology
KY12065/Research Project of Hubei University of Science and Technology
Q20172802/Research Project of Hubei Provincial Department of Education
*Corresponding Author(s):  HONGBING CAI     E-mail:  chb20105@sina.com

Cite this article: 

L. Xu, H. Cai, N. Zhu, Bo Zheng. Interleukin-22 derived from cervical cancer-associated fibroblasts accelerates senescence of normal fibroblasts and promotes expression of tumorigenesis-related factors in HeLa cells. European Journal of Gynaecological Oncology, 2020, 41(2): 192-199.

URL: 

https://ejgo.imrpress.com/EN/10.31083/j.ejgo.2020.02.4970     OR     https://ejgo.imrpress.com/EN/Y2020/V41/I2/192

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