title: Gene methylation of human ovarian carcinoma stromal progenitor cells promotes tumorigenesis.
abstract: BACKGROUND
  This study aimed to investigate whether the DNA methylation of human ovarian carcinoma stromal progenitor cells (OCSPCs) could promote the tumorigenesis of ovarian carcinoma.
  
  
  METHODS
  OCSPCs were first isolated from fresh tumor tissues and ascites of ovarian cancer patients. In vivo and in vitro experiments on the effect of the OCSPCs on tumorigenesis and the effects of DNA demethylation on the OCSPCs were then performed.
  
  
  RESULTS
  The OCSPCs possessed self-renewal and multipotent differentiation capacity with elevated expressions of OCT4, NANOG, BMP2, BMP4, Rex-1, AC133 and TGF-β. The OCSPCs, when combined with tumor cells in vivo could promote tumor growth. The methylation profiles of tumor suppressor genes (TSGs) were significantly higher in the OCSPCs than in ovarian cancer cells (p < 0.001). 5-aza-2-dC could alter the methylation levels of TSGs in OCSPCs and also inhibit the tumor promoting capabilities of the OCSPCs by decreasing the proliferation of tumors cells. The expression levels of TSGs were re-expressed by 5-aza-2-dC to inhibit the self-renewal and growth of OCSPCs.
  
  
  CONCLUSIONS
  OCSPCs with decreased TSG expressions in the ovarian tumor microenvironment were able to promote tumorigenesis which could be reversed by DNA demethylation. DNA demethylation reversing the expression of TSGs in OCSPCs may represent a potential therapeutic target for ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Gynecologic Cancer Center, Cathay General Hospital, Taipei, Taiwan. cmho@cgh.org.tw.|School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City, Taiwan. cmho@cgh.org.tw.|School of Medicine, Taipei Medical University, Taipei, Taiwan. cmho@cgh.org.tw.
authors.forename: Chih-Ming
authors.initials: CM
authors.lastname: Ho
authors.affiliation: Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, #250 Wu-Hsing Street, Taipei, 110, Taiwan. tzubi34@gmail.com.|Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan. tzubi34@gmail.com.
authors.forename: Daniel Tzu-Bi
authors.initials: DT
authors.lastname: Shih
authors.affiliation: Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, #250 Wu-Hsing Street, Taipei, 110, Taiwan. ansonsfaith@gmail.com.
authors.forename: Chih-Chiang
authors.initials: CC
authors.lastname: Hsiao
authors.affiliation: Department of Pathology, Cathay General Hospital, Taipei, Taiwan. drshhuang@gmail.com.
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, #250 Wu-Hsing Street, Taipei, 110, Taiwan. cmbsfc21@tmu.edu.tw.
authors.forename: Shwu-Fen
authors.initials: SF
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, National Taiwan University, #7 Chung-Shan South Road, Taipei, 100, Taiwan. wenfangcheng@yahoo.com.|Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan. wenfangcheng@yahoo.com.|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. wenfangcheng@yahoo.com.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Cheng
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D063646:Carcinogenesis; D002454:Cell Differentiation; D019070:Cell Lineage; D019175:DNA Methylation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor