Oncotarget

Research Papers:

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

Dan Wang, Tong Xiang, Zhongquan Zhao, Kailong Lin, Pin Yin, Lupin Jiang, Zhiqing Liang _ and Bo Zhu

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Oncotarget. 2016; 7:76006-76020. https://doi.org/10.18632/oncotarget.12579

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Abstract

Dan Wang1,*, Tong Xiang2,3,*, Zhongquan Zhao4,*, Kailong Lin2, Pin Yin1, Lupin Jiang1, Zhiqing Liang1, Bo Zhu2

1Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

2Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China

3Department of Oncology, No. 421 Hospital of PLA, Guangzhou 510318, China

4Department 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.


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