CD133+ ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition
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Haixia Long1,*, Tong Xiang1,*, Wei Qi1, Jiani Huang1, Junying Chen1, Luhang He1, Zhiqing Liang2, Bo Guo1, Yongsheng Li1, Rongkai Xie3 and Bo Zhu1,4
1 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
2 Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, China
3 Department of Obstetrics and Gynecology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
4 Biomedical Analysis Center, Third Military Medical University, Chongqing, China
* These authors contributed equally to this work
Bo Zhu, email:
Rongkai Xie, email:
Keywords: cancer stem like cells, non-cancer stem like cells, chemokine (C-C motif) ligand 5, epithelial-mesenchymal transition, NF-κB
Received: October 14, 2014 Accepted: January 20, 2015 Published: February 28, 2015
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.
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