Autocrine interleukin-23 promotes self-renewal of CD133 + ovarian cancer stem-like cells

// Dan Wang 1, * , Tong Xiang 2, 3, * , Zhongquan Zhao 4, * , Kailong Lin 2 , Pin Yin 1 , Lupin Jiang 1 , Zhiqing Liang 1 , Bo Zhu 2 1 Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China 2 Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China 3 Department of Oncology, No. 421 Hospital of PLA, Guangzhou 510318, China 4 Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian 350025, China * These authors have contributed equally to this work Correspondence to: Zhiqing Liang, email: zhi_lzliang@163.com Bo Zhu, email: oncology_bozhu@yahoo.com.cn Keywords: cancer stem cells, IL-23, self-renewal, ovarian cancer Received: February 25, 2016     Accepted: August 24, 2016     Published: October 12, 2016 ABSTRACT Cancer stem cells (CSCs) are a group of cells which possess the ability of self-renewing and unlimited proliferation. And these CSCs are thought to be the cause of metastasis, recurrence and resistance. Recent study has found that pro-inflammatory cytokine and chemotactic factor mediate the self-renewing and differentiation of most of CSCs. Thus we speculate that ovarian cancer stem cells (OCSCs) can also maintain the ability of self-renewing and differentiation by releasing inflammatory factor. This report we discuss the biological characteristics and the specific molecular mechanism mediated by interleukin-23 (IL-23) and its receptor on the self-renewing of OCSCs. We found that OCSCs had high expression of IL-23 and IL-23R. IL-23 could promote the self-renewal ability of OCSCs and played a very important role to maintain the stable expression of stem cell markers in vitro. Moreover, we verified that IL-23 could maintain the potential tumorigenic of OCSCs in vivo and mediate the self-renewal ability and the formation of tumor in OCSCs by activating the signal pathways of STAT3 and NF-κB. In addition, human low differentiation tissues showed overexpression of IL-23. And IL-23 positively correlated to the expression level of CD133, Nanog and Oct4. In conclusion, Our discoveries demonstrate that autocrine IL-23 contribute to ovarian cancer malignancy through promoting the self-renewal of CD133 + ovarian cancer stem-like cells, and this suggests that IL-23 and its signaling pathway might serve as therapeutic targets for the treatment of ovarian cancer.