title: Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion.
abstract: OBJECTIVE
  In recent years, the Wnt signalling pathway has been implicated in epithelial ovarian cancer and its members have potential as diagnostic, prognostic and therapeutic targets. Here we investigated the role of two Wnt receptor tyrosine kinases (RTKs), ROR1 and ROR2, and their putative ligand, Wnt5a, in ovarian cancer.
  
  
  METHODS
  Immunohistochemistry for ROR2 was performed in a large patient cohort, including benign controls, borderline tumours and epithelial ovarian cancer. In addition, siRNA was used to silence ROR1, ROR2 and Wnt5a individually, and together, in two ovarian cancer cell lines, and the effects on cell proliferation, adhesion, migration and invasion were measured.
  
  
  RESULTS
  ROR2 expression is significantly increased in ovarian cancer patients compared to patients with benign disease. In vitro assays showed that silencing either receptor inhibits ovarian cancer cell migration and invasion, and concurrently silencing both receptors has an even stronger inhibitory effect on proliferation, migration and invasion.
  
  
  CONCLUSIONS
  ROR2 expression is increased in epithelial ovarian cancer, and silencing ROR2 and its sister receptor ROR1 has a strong inhibitory effect on the ability of ovarian cancer cells to proliferate, migrate and invade through an extracellular matrix.
authors.affiliation: Metastasis Research Group, Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, New South Wales, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Henry
authors.affiliation: Metastasis Research Group, Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, New South Wales, Australia.
authors.forename: Estelle
authors.initials: E
authors.lastname: Llamosas
authors.affiliation: Department of Gynecology and Gynecological Oncology, Hospital for Women, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Knipprath-Meszaros
authors.affiliation: Department of Gynecology and Gynecological Oncology, Hospital for Women, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schoetzau
authors.affiliation: Department of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Ellen
authors.initials: E
authors.lastname: Obermann
authors.affiliation: Department of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Maya
authors.initials: M
authors.lastname: Fuenfschilling
authors.affiliation: Department of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Caduff
authors.affiliation: Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.affiliation: Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, Australia.
authors.forename: Neville
authors.initials: N
authors.lastname: Hacker
authors.affiliation: Department of Research, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Robyn
authors.initials: R
authors.lastname: Ward
authors.affiliation: Department of Gynecology and Gynecological Oncology, Hospital for Women, University Hospital Basel, University of Basel, Basel, Switzerland.
authors.forename: Viola
authors.initials: V
authors.lastname: Heinzelmann-Schwarz
authors.affiliation: Metastasis Research Group, Adult Cancer Program, Lowy Cancer Research Centre and Prince of Wales Clinical School, Faculty of Medicine, University of New South Wales, New South Wales, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ford
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C078716:ROR1 protein, human; C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors
keywords: ROR1; ROR2; Wnt signalling; epithelial ovarian cancer; metastasis