title: CD133+ ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition.
abstract: Cancer stem cells (CSCs, also called cancer stem-like cells, CSLCs) can function as "seed cells" for tumor recurrence and metastasis. Here, we report that, in the presence of CD133+ ovarian CSLCs, CD133- non-CSLCs can undergo an epithelial-mesenchymal transition (EMT)-like process and display enhanced metastatic capacity in vitro and in vivo. Highly elevated expression of chemokine (C-C motif) ligand 5 (CCL5) and its receptors chemokine (C-C motif) receptor (CCR) 1/3/5 are observed in clinical and murine metastatic tumor tissues from epithelial ovarian carcinomas. Mechanistically, paracrine CCL5 from ovarian CSLCs activates the NF-κB signaling pathway in ovarian non-CSLCs via binding CCR1/3/5, thereby inducing EMT and tumor invasion. Taken together, our results redefine the metastatic potential of non-stem cancer cells and provide evidence that targeting the CCL5:CCR1/3/5-NF-κB pathway could be an effective strategy to prevent ovarian cancer metastasis.
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Haixia
authors: H
authors: Long
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Tong
authors: T
authors: Xiang
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Wei
authors: W
authors: Qi
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Jiani
authors: J
authors: Huang
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Junying
authors: J
authors: Chen
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Luhang
authors: L
authors: He
authors: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Zhiqing
authors: Z
authors: Liang
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Bo
authors: B
authors: Guo
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Yongsheng
authors: Y
authors: Li
authors: Department of Obstetrics and Gynecology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors: Rongkai
authors: R
authors: Xie
authors: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.|Biomedical Analysis Center, Third Military Medical University, Chongqing, China.
authors: Bo
authors: B
authors: Zhu
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides; D015398:Signal Transduction
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C483024:CCL5 protein, human; C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse
keywords: NF-κB; cancer stem like cells; chemokine (C-C motif) ligand 5; epithelial-mesenchymal transition; non-cancer stem like cells