China Oncology ›› 2014, Vol. 24 ›› Issue (4): 252-257.doi: 10.3969/j.issn.1007-3969.2014.04.003

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Cancer-associated fibroblasts promotes migration and invasion of cervical epithelial cancer cells through IL-6-induced “epithelial-mesenchymal” transition

REN Chun-xia1, ZHAO Min2, XU Na1, SONG Ya-qin1, CHEN Ya-ping3, LV Bei1, YANG Gong4,5   

  1. 1.Department of Gynecology and Obstetrics, The People’s Hospital of Wuxi, Wuxi Jiangsu 214023, China; 2.Department of Gynecology and Obstetrics, Shandong Jiaotong Hospital, Jinan Shandong 250031, China; 3.The 5th People’s Hospital of Shanghai, Fudan University, Department of Gynecology and Obstetrics, Shanghai Medical College, Fudan University, Shanghai 200240, China; 4.Central Laboratory, The 5th People’s Hospital of Shanghai, Fudan University, Department of Gynecology and Obstetrics, Shanghai Medical College, Fudan University, Shanghai 200240, China; 5.Cancer Institute, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Online:2014-04-30 Published:2014-05-06
  • Contact: LV Bei E-mail: lvbei@wuxiph.com

Abstract:

Background and purpose: Cancer-associated fibroblasts (CAFs) are known to promote the invasion and metastasis of epithelial cancers. The cytokine IL-6 may mediate the interaction between stromal cells and epithelia in tumor microenvironment to facilitate the invasiveness and metastasis of cancer, however, such mechanism has not been fully covered yet. Methods: We used cervical cancer cell line HeLa as a model for this study. ELISA was used to measure the levels of IL-6 in CAFs and normal fibroblasts (NFs) isolated from squamous cervical cancer or normal cervical tissues. CAFs conditioned medium or IL-6 was used to treat cervical cancer HeLa cell line. The epithelial-mesenchymal transition (EMT) markers such as N-Cadherin and Vimentin were detected by Western blot in cells before and after treatment. Scratches and transwell chambers were used to test the abilities of cell migration and invasion. Results: The levels of IL-6 were 4-5 folds higher in CAFs than in NFs. Treatment of HeLa cells with CAF conditioned medium or IL-6 upregulated N-Cadherin and Vimentin, but down-regulated E-Cadherin and cytokeratin, compared with control cells, indicating that IL-6 may stimulate HeLa cells to EMT. Further study found that Snail 1, the featured transcription factor for stem cells, was increased along with the enhanced phosphorylation of STAT3. Meanwhile, the migration and invasion of HeLa cells treated with IL-6 or CAF conditioned medium were markedly increased. Conclusion: CAF induces the EMT of cervical epithelial cancer cells through IL-6/STAT3/Snail pathway, which thereby promotes the invasiveness and metastasis cervical epithelial cancer.

Key words: Cancer-associated fibroblasts, Cervical cancer, Interleukin-6, Epithelial-mesenchymal transition, Migration and invasion