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

Cancer-associated fibroblasts (CAFs) are closely related to epithelial-mesenchymal transition (EMT) and chemoresistance in various cancers. Experiments and retrospective studies were applied to explore the role of CAFs in epithelial ovarian cancer (EOC). 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. CAFs may activate the Wnt/β-catenin pathway in EOC cells via CXCL12/CXCR4 axis, and then induce EMT and cisplatin resistance.