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

// Haixia Long 1,* , Tong Xiang 1,* , Wei Qi 1 , Jiani Huang 1 , Junying Chen 1 , Luhang He 1 , Zhiqing Liang 2 , Bo Guo 1 , Yongsheng Li 1 , Rongkai Xie 3 and Bo Zhu 1,4 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.