title: Cell line and patient-derived xenograft models reveal elevated CDCP1 as a target in high-grade serous ovarian cancer.
abstract: BACKGROUND
  Development of targeted therapies for high-grade serous ovarian cancer (HGSC) remains challenging, as contributing molecular pathways are poorly defined or expressed heterogeneously. CUB-domain containing protein 1 (CDCP1) is a cell-surface protein elevated in lung, colorectal, pancreas, renal and clear cell ovarian cancer.
  
  
  METHODS
  CUB-domain containing protein 1 was examined by immunohistochemistry in HGSC and fallopian tube. The impact of targeting CDCP1 on cell growth and migration in vitro, and intraperitoneal xenograft growth in mice was examined. Three patient-derived xenograft (PDX) mouse models were developed and characterised for CDCP1 expression. The effect of a monoclonal anti-CDCP1 antibody on PDX growth was examined. Src activation was assessed by western blot analysis.
  
  
  RESULTS
  Elevated CDCP1 was observed in 77% of HGSC cases. Silencing of CDCP1 reduced migration and non-adherent cell growth in vitro and tumour burden in vivo. Expression of CDCP1 in patient samples was maintained in PDX models. Antibody blockade of CDCP1 significantly reduced growth of an HGSC PDX. The CDCP1-mediated activation of Src was observed in cultured cells and mouse xenografts.
  
  
  CONCLUSIONS
  CUB-domain containing protein 1 is over-expressed by the majority of HGSCs. In vitro and mouse model data indicate that CDCP1 has a role in HGSC and that it can be targeted to inhibit progression of this cancer.
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.|Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.
authors.forename: Brittney S
authors.initials: BS
authors.lastname: Harrington
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.|Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.
authors.forename: Yaowu
authors.initials: Y
authors.lastname: He
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.|Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Davies
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Wallace
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Adams
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Beaven
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.|Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.
authors.forename: Deborah K
authors.initials: DK
authors.lastname: Roche
authors.affiliation: Department of Gynaecological Oncology, Westmead Hospital and Centre for Cancer Research, Westmead Millennium Institute, Westmead, NSW 2145, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kennedy
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Naven P
authors.initials: NP
authors.lastname: Chetty
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Crandon
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Flatley
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Niara B
authors.initials: NB
authors.lastname: Oliveira
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Shannon
authors.affiliation: Department of Gynaecological Oncology, Westmead Hospital and Centre for Cancer Research, Westmead Millennium Institute, Westmead, NSW 2145, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: deFazio
authors.affiliation: Cheryl Brown Ovarian Cancer Outcomes Unit, Division of Medical Oncology and Vancouver Centre, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Tinker
authors.affiliation: Department of Pathology and Laboratory Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba, QLD 4102, Australia.
authors.forename: Brian
authors.initials: B
authors.lastname: Gabrielli
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Donal J
authors.initials: DJ
authors.lastname: Brennan
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.|Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Jermaine I
authors.initials: JI
authors.lastname: Coward
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Armes
authors.affiliation: Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.|Mater Health Services, South Brisbane, QLD 4101, Australia.
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Perrin
authors.affiliation: Mater Research Institute, University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.|Mater Ovarian Cancer Research Collaborative, Mater Adult Hospital, South Brisbane, QLD 4101, Australia.
authors.forename: John D
authors.initials: JD
authors.lastname: Hooper
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C432044:CDCP1 protein, human; D015815:Cell Adhesion Molecules; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering