Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion
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Claire Henry1, Estelle Llamosas1, Alexandra Knipprath-Meszaros2, Andreas Schoetzau2, Ellen Obermann3, Maya Fuenfschilling3, Rosemarie Caduff4, Daniel Fink5, Neville Hacker6, Robyn Ward7, Viola Heinzelmann-Schwarz2, Caroline Ford1
1Metastasis 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
2Department of Gynecology and Gynecological Oncology, Hospital for Women, University Hospital Basel, University of Basel, Basel, Switzerland
3Department of Pathology, University Hospital Basel, University of Basel, Basel, Switzerland
4Department of Pathology, University Hospital Zurich, Zurich, Switzerland
5Department of Gynecology, University Hospital Zurich, Zurich, Switzerland
6Gynaecological Cancer Centre, Royal Hospital for Women, Sydney, Australia
7Department of Research, The University of Queensland, Brisbane, Queensland, Australia
Caroline Ford, e-mail: [email protected]
Keywords: ROR2, ROR1, Wnt signalling, epithelial ovarian cancer, metastasis
Received: May 21, 2015 Accepted: October 08, 2015 Published: October 20, 2015
AIM: 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.
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