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

任春霞; 赵敏; 徐娜; 宋亚琴; 陈亚萍; 吕蓓; 杨恭

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

更新时间：2025-12-31

- Cancer-associated fibroblasts promotes migration and invasion of cervical epithelial cancer cells through IL-6-induced “epithelial-mesenchymal” transition
- China Oncology Vol. 24, Issue 4, Pages: 252-257(2014)
- 作者机构：
  
  1. 江苏省无锡市人民医院妇产科,江苏,无锡,214023
  2. 山东省交通医院妇产科,山东,济南,250031
  3. 复旦大学附属上海市第五人民医院妇产科，复旦大学上海医学院妇产科学系,上海,200240
  4. 复旦大学附属上海市第五人民医院中心实验室，复旦大学上海医学院妇产科学系,上海,200240
  5. 复旦大学附属肿瘤医院肿瘤研究所，复旦大学上海医学院肿瘤学系,上海,200032
- 作者简介：
- 基金信息：
- DOI：10.3969/j.issn.1007-3969.2014.04.003
  CLC：
- Published Online：06 May 2014，
  
  Published：06 May 2014
- 稿件说明：
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任春霞,赵敏,徐娜,宋亚琴,陈亚萍,吕蓓,杨恭. 癌相关成纤维细胞通过IL-6诱导的“上皮-间质”转换促进宫颈癌细胞的迁移和侵袭[J]. 中国癌症杂志, 2014, 24(4): 252-257.

任春霞, 赵敏, 徐娜, et al. Cancer-associated fibroblasts promotes migration and invasion of cervical epithelial cancer cells through IL-6-induced “epithelial-mesenchymal” transition[J]. China Oncology, 2014, 24(4): 252-257.
任春霞,赵敏,徐娜,宋亚琴,陈亚萍,吕蓓,杨恭. 癌相关成纤维细胞通过IL-6诱导的“上皮-间质”转换促进宫颈癌细胞的迁移和侵袭[J]. 中国癌症杂志, 2014, 24(4): 252-257. DOI： 10.3969/j.issn.1007-3969.2014.04.003.

任春霞, 赵敏, 徐娜, et al. Cancer-associated fibroblasts promotes migration and invasion of cervical epithelial cancer cells through IL-6-induced “epithelial-mesenchymal” transition[J]. China Oncology, 2014, 24(4): 252-257. DOI： 10.3969/j.issn.1007-3969.2014.04.003.

摘要

背景与目的：癌相关成纤维细胞(cancer-associated fibroblasts，CAFs)能促进上皮肿瘤的侵袭和转移，细胞因子IL-6在肿瘤间质微环境中可能介导间质和上皮的相互作用，促进肿瘤的侵袭和转移，但其具体机制尚不十分清楚。方法：以宫颈癌细胞HeLa为研究模型，用ELISA测定宫颈癌CAFs和正常宫颈组织成纤维细胞(normal fibroblasts，NFs)条件培养基中IL-6的表达；用条件培养基或IL-6分别处理宫颈癌细胞系HeLa；用Western blot测定样品处理前后上皮-间质转化(epithelial-mesenchymal transition，EMT)标志物(如N-Cadherin和Vimentin等)的变化，同时用划痕和transwell小室测定细胞迁移和侵袭能力的变化。结果：CAF中IL-6表达比NF高4～5倍；与对照组相比，用CAF条件培养基或IL-6处理的HeLa细胞间充质细胞标志物Vimentin和N-Cadherin升高，而上皮细胞标志物E-Cadherin和Cytokeratin下降，表明IL-6可以促进细胞的EMT发生；进一步研究发现过量IL-6处理的HeLa细胞中干细胞转录因子Snail 1随STAT3的激活而上升；同时发现过量IL-6处理的HeLa细胞的迁移和侵袭能力大幅增加。结论：CAF在肿瘤微环境中可能通过IL-6/STAT3/Snail通路诱导宫颈癌上皮细胞的EMT转化，从而促进宫颈癌的侵袭和转移能力。

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.

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