title: Autocrine interleukin-23 promotes self-renewal of CD133+ ovarian cancer stem-like cells.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.|Department of Oncology, No. 421 Hospital of PLA, Guangzhou 510318, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Xiang
authors.affiliation: Department of Oncology, Fuzhou General Hospital, Fuzhou, Fujian 350025, China.
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Kailong
authors.initials: K
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Lupin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism*; D000818:Animals; D019898:Autocrine Communication; D015415:Biomarkers; D045744:Cell Line, Tumor; D000066673:Cell Self Renewal / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000071916:AC133 Antigen; D015415:Biomarkers; C515500:IL23R protein, human; D053759:Interleukin-23; C486780:NANOG protein, human; D016328:NF-kappa B; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor
keywords: IL-23; cancer stem cells; ovarian cancer; self-renewal