Cancer-Associated Fibroblast-Derived Interleukin-8 Promotes Ovarian Cancer Cell Stemness and Malignancy Through the Notch3-Mediated Signaling

doi:10.3389/fcell.2021.684505

	Cancer-Associated Fibroblast-Derived Interleukin-8 Promotes Ovarian Cancer Cell Stemness and Malignancy Through the Notch3-Mediated Signaling
	Ji, Zhaodong 4,5; Tian, Wenjuan 1,4,5; Gao, Wen 6; Zang, Rongyu 2; Wang, Huaying 1,5; Yang, Gong 3,4,5
刊名	FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
	2021-07-01
卷号	9
关键词	IL-8 tumor stemness epithelial ovarian cancer cancer-associated ovarian fibroblasts Notch3 signal pathway
ISSN号	2296-634X
DOI	10.3389/fcell.2021.684505
通讯作者	Zang, Rongyu(zang.rongyu@zs-hospital.sh.cn) ; Wang, Huaying(huaying2004@shca.org.cn) ; Yang, Gong(yanggong@fudan.edu.cn)
英文摘要	As a significant component in ovarian cancer microenvironment, cancer-associated fibroblasts (CAFs) contribute to cancer progression through interaction with cancer cells. Recent studies demonstrate that interleukin-8 (IL-8) is overexpressed in multiple cancer types and is essential for tumor development. Nonetheless, the underlying mechanism that the CAF-derived IL-8 promotes ovarian tumorigenesis is unknown. Here, we show that IL-8 secreted from CAFs could activate normal ovarian fibroblasts (NFs) through multiple signaling and that IL-8 stimulated malignant growth of ovarian cancer cells in animals and increased the IC50 of cisplatin (CDDP) in ovarian cancer cells. Further study showed that IL-8 induced cancer cell stemness via the activation of Notch3 and that the high level of IL-8 in ascites was positively correlated with the expression of Notch3 in ovarian cancer tissues. Collectively, IL-8 secreted from CAFs and cancer cells promotes stemness in human ovarian cancer via the activation of the Notch3-mediated signaling, which may provide a novel strategy for ovarian cancer treatment.
资助项目	National Natural Science Foundation of China[81572553] ; National Natural Science Foundation of China[81372797] ; National Natural Science Foundation of China[81772789] ; National Natural Science Foundation of China[81171911] ; National Natural Science Foundation of China[82002758]
WOS关键词	ENDOTHELIAL-CELLS ; TARGETING NOTCH ; GROWTH-FACTOR ; TUMOR-CELLS ; TUMORIGENESIS ; INHIBITION ; SENESCENCE ; DLL4
WOS研究方向	Cell Biology ; Developmental Biology
语种	英语
出版者	FRONTIERS MEDIA SA
WOS记录号	WOS:000673597500001
资助机构	National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/123296]
专题	中国科学院合肥物质科学研究院
通讯作者	Zang, Rongyu; Wang, Huaying; Yang, Gong
作者单位	1.Fudan Univ, Shanghai Canc Ctr, Gynecol Oncol, Shanghai, Peoples R China 2.Fudan Univ, Zhongshan Hosp, Dept Obstet & Gynecol, Ovarian Canc Program,Div Gynecol Oncol, Shanghai, Peoples R China 3.Fudan Univ, Peoples Hosp Shanghai 5, Cent Lab, Shanghai, Peoples R China 4.Fudan Univ, Shanghai Canc Ctr, Inst Canc, Shanghai, Peoples R China 5.Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China 6.Chinese Acad Sci, Univ Chinese Acad Sci, Inst Basic Med & Canc IBMC, Canc Hosp,Zhejiang Canc Hosp, Hangzhou, Peoples R China
推荐引用方式 GB/T 7714	Ji, Zhaodong,Tian, Wenjuan,Gao, Wen,et al. Cancer-Associated Fibroblast-Derived Interleukin-8 Promotes Ovarian Cancer Cell Stemness and Malignancy Through the Notch3-Mediated Signaling[J]. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,2021,9.
APA	Ji, Zhaodong,Tian, Wenjuan,Gao, Wen,Zang, Rongyu,Wang, Huaying,&Yang, Gong.(2021).Cancer-Associated Fibroblast-Derived Interleukin-8 Promotes Ovarian Cancer Cell Stemness and Malignancy Through the Notch3-Mediated Signaling.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9.
MLA	Ji, Zhaodong,et al."Cancer-Associated Fibroblast-Derived Interleukin-8 Promotes Ovarian Cancer Cell Stemness and Malignancy Through the Notch3-Mediated Signaling".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9(2021).