Journal
FUTURE ONCOLOGY
Volume 16, Issue 32, Pages 2619-2633Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/fon-2020-0095
Keywords
apoptosis; beta-catenin; CAFs; cisplatin resistance; CXCL12; CXCR4; EMT; ovarian cancer; Wnt
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Funding
- Natural Science Foundation of Shandong Province [ZR2019PH111]
- projects of medical and health technology development program in Shandong province [2019WS489]
- Science Foundation of Shandong Academy of Medical Sciences [2018-35]
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Aim:Cancer-associated fibroblasts (CAFs) are closely related to epithelial-mesenchymal transition (EMT) and chemoresistance in various cancers.Patients & methods:Experimentsin vivoand 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/beta-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/beta-catenin pathway in EOC cells via CXCL12/CXCR4 axis, and then induce EMT and cisplatin resistance.
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