title: Secreted frizzled-related protein 4 expression is positively associated with responsiveness to cisplatin of ovarian cancer cell lines in vitro and with lower tumour grade in mucinous ovarian cancers.
abstract: BACKGROUND
  Ovarian cancer is one of the most lethal malignancies in women, as it is frequently detected at an advanced stage, and cancers often become refractory to chemotherapy. Evidence suggests that dysregulation of pro-apoptotic genes plays a key role in the onset of chemoresistance. The secreted Frizzled-Related Protein (sFRP) family is pro-apoptotic and also a negative modulator of the Wnt signalling cascade. Studies have demonstrated that the re-expression of sFRPs, in particular sFRP4, is associated with a better prognosis, and that experimentally induced expression results in cell death.
  
  
  RESULTS
  In vitro experimental models determined that sFRP4 was differentially expressed in chemosensitive (A2780) and chemoresistant (A2780 ADR and A2780 Cis) ovarian cell lines, with chemosensitive cells expressing significantly higher levels of sFRP4. Transfection of the chemoresistant cell lines with sFRP4 significantly increased their sensitivity to chemotherapy. Conversely, silencing of sFRP4 expression in the chemosensitive cell line resulted in a corresponding increase in chemoresistance. Comparison of sFRP4 expression in tumour biopsies revealed a positive trend between sFRP4 expression and tumour grade, with mucinous cyst adenocarcinomas exhibiting significantly decreased sFRP4 levels compared to mucinous borderline tumours.
  
  
  CONCLUSIONS
  This study indicates a role for sFRP4 as a predictive marker of chemosensitivity in ovarian cancer and suggests that this pathway may be worth exploiting for novel therapies.
authors.affiliation: School of Anatomy and Human Biology, Faculty of Life and Physical Sciences, The University of Western Australia, Perth, Crawley, Western Australia.
authors.forename: Uttara
authors.initials: U
authors.lastname: Saran
authors.forename: Frank
authors.initials: F
authors.lastname: Arfuso
authors.forename: Nikolajs
authors.initials: N
authors.lastname: Zeps
authors.forename: Arunasalam
authors.initials: A
authors.lastname: Dharmarajan
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins