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Oncotarget. 2016 Nov 15;7(46):76006-76020. doi: 10.18632/oncotarget.12579.

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

Author information

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.

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.

KEYWORDS:

IL-23; cancer stem cells; ovarian cancer; self-renewal

PMID:
27738346
PMCID:
PMC5342794
DOI:
10.18632/oncotarget.12579
[Indexed for MEDLINE]
Free PMC Article

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