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。
Targeting the ROR1 and ROR2 receptors in epithelial ovarian cancer inhibits cell migration and invasion.
作者信息
Henry Claire, Llamosas Estelle, Knipprath-Meszaros Alexandra, Schoetzau Andreas, Obermann Ellen, Fuenfschilling Maya, Caduff Rosemarie, Fink Daniel, Hacker Neville, Ward Robyn, Heinzelmann-Schwarz Viola, Ford Caroline
机构信息
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.
Department of Gynecology and Gynecological Oncology, Hospital for Women, University Hospital Basel, University of Basel, Basel, Switzerland.
出版信息
Oncotarget. 2015 Nov 24;6(37):40310-26. doi: 10.18632/oncotarget.5643.
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.
目的
近年来，Wnt信号通路与上皮性卵巢癌有关，其成员具有作为诊断、预后和治疗靶点的潜力。在此，我们研究了两种Wnt受体酪氨酸激酶（RTK），即ROR1和ROR2，及其假定配体Wnt5a在卵巢癌中的作用。
方法
对包括良性对照、交界性肿瘤和上皮性卵巢癌在内的一大组患者进行ROR2免疫组织化学检测。此外，在两种卵巢癌细胞系中分别或联合使用小干扰RNA（siRNA）沉默ROR1、ROR2和Wnt5a，并检测其对细胞增殖、黏附、迁移和侵袭的影响。
结果
与良性疾病患者相比，卵巢癌患者的ROR2表达显著增加。体外实验表明，沉默任一受体均可抑制卵巢癌细胞的迁移和侵袭，同时沉默两种受体对增殖、迁移和侵袭具有更强的抑制作用。
结论
上皮性卵巢癌中ROR2表达增加，沉默ROR2及其姊妹受体ROR1对卵巢癌细胞通过细胞外基质增殖、迁移和侵袭的能力具有强烈抑制作用。
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