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

被引：75
作者：
Zhang, Fang [1 ,2 ]
Cui, Jian-ying [3 ]
Gao, Hai-feng [4 ]
Yu, Hao [5 ]
Gao, Fu-feng [5 ]
Chen, Jin-long [5 ]
Chen, Liang [5 ]
机构：
[1] Shandong Univ, Dept Radiol, Prov Hosp, Jinan 250021, Peoples R China
[2] Shandong First Med Univ, Dept Radiol, Shandong Prov Hosp, Jinan 250021, Peoples R China
[3] Jiyang Dist Peoples Hosp Jinan City, Dept Obstet & Gynecol, Jinan 251400, Peoples R China
[4] Dongying Peoples Hosp, Dept Oncol, Dongying 257091, Shandong, Peoples R China
[5] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Gynecol Oncol, Jinan 250117, Peoples R China
来源：
FUTURE ONCOLOGY | 2020年 / 16卷 / 32期
关键词：
apoptosis; beta-catenin; CAFs; cisplatin resistance; CXCL12; CXCR4; EMT; ovarian cancer; Wnt; WNT/BETA-CATENIN PATHWAY; COLORECTAL-CANCER; TUMOR-GROWTH; METASTASIS; CHEMORESISTANCE; INVASION; ANGIOGENESIS;
D O I：
10.2217/fon-2020-0095
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：2619 / 2633
页数：15
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