Oncotarget

Research Papers:

CD133+ ovarian cancer stem-like cells promote non-stem cancer cell metastasis via CCL5 induced epithelial-mesenchymal transition

Haixia Long, Tong Xiang, Wei Qi, Jiani Huang, Junying Chen, Luhang He, Zhiqing Liang, Bo Guo, Yongsheng Li, Rongkai Xie and Bo Zhu _

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Oncotarget. 2015; 6:5846-5859. https://doi.org/10.18632/oncotarget.3462

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Abstract

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

Correspondence to:

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

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.


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