Research Article

Cancer-associated fibroblasts induce epithelial-mesenchymal transition and cisplatin resistance in ovarian cancer via CXCL12/CXCR4 axis

Department of Radiology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, PR China

Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, PR China

^‡Zhang Fang and Jian-ying Cui contributed equally to this study and are co-first authors

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Jian-ying Cui^‡

Department of Obstetrics & Gynecology, Jiyang District People's Hospital of Jinan City, Jinan 251400, PR China

^‡Zhang Fang and Jian-ying Cui contributed equally to this study and are co-first authors

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Hai-feng Gao

Department of Oncology, Dongying People's Hospital, Dongying, Shandong 257091, PR China

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Hao Yu

Department of Gynecological Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China

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Fu-feng Gao

Department of Gynecological Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China

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Jin-long Chen

Department of Gynecological Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China

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Liang Chen

*Author for correspondence: Tel.: +86 0531 6762 6546; +86 159 6562 5931; Fax: 86 0531 6762 6546;

E-mail Address: 155338644@qq.com

https://orcid.org/0000-0003-4274-8933

Department of Gynecological Oncology, Shandong Cancer Hospital & Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, PR China

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Published Online:17 Aug 2020https://doi.org/10.2217/fon-2020-0095

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Abstract

Aim: Cancer-associated fibroblasts (CAFs) are closely related to epithelial-mesenchymal transition (EMT) and chemoresistance in various cancers. Patients & methods: Experiments in vivo and retrospective studies were applied to explore the role of CAFs in epithelial ovarian cancer (EOC). Results: We found that CXCL12 expression was significantly increased in interstitial CAFs by immunofluorescence. CAF-derived CXCL12 induced EMT though CXCR4/Wnt/β-catenin pathway in EOC cells. Inhibited EMT led to increased apoptosis and cisplatin sensitivity. Multivariate regression analysis shows that CXCL12 expression in the stromal cells and cytoreduction satisfaction are independent prognostic markers of platinum-containing chemotherapy sensitivity in 296 EOC patients. Conclusion: CAFs may activate the Wnt/β-catenin pathway in EOC cells via CXCL12/CXCR4 axis, and then induce EMT and cisplatin resistance.

Keywords:

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Vol. 16, No. 32

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History

Received 7 February 2020

Accepted 17 July 2020

Published online 17 August 2020

Published in print November 2020

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Financial & competing interests disclosure

This study was financially supported by the Natural Science Foundation of Shandong Province (grant ZR2019PH111), projects of medical and health technology development program in Shandong province (grant 2019WS489) and the Science Foundation of Shandong Academy of Medical Sciences (grant 2018-35). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

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