Interleukin-22 derived from cervical cancer-associated fibroblasts accelerates senescence of normal fibroblasts and promotes expression of tumorigenesis-related factors in HeLa cells

摘要

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 beta-galactosidase (SA beta-gal). Expression of alpha-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 alpha-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 MIMP9 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.