Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion

靶向上皮性卵巢癌中的 ROR1 和 ROR2 受体可抑制细胞迁移和侵袭

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作者:Claire Henry, Estelle Llamosas, Alexandra Knipprath-Meszaros, Andreas Schoetzau, Ellen Obermann, Maya Fuenfschilling, Rosemarie Caduff, Daniel Fink, Neville Hacker, Robyn Ward, Viola Heinzelmann-Schwarz, Caroline Ford

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.

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.

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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