Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma
Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma
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DOI：
10.1111/j.1349-7006.2009.01165.x
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发表时间：
2009-07-01
期刊：
影响因子：
5.7
通讯作者：
Matsuda, Koichi
中科院分区：
文献类型：
--
作者：
Morioka, Kazuhito;Tanikawa, Chizu;Matsuda, Koichi
骨肉瘤是儿童和青少年最常见的骨恶性肿瘤，具有组织学异质性和高远处转移倾向。尽管在过去的几十年里，辅助化疗显着改善了治疗效果，但骨肉瘤肺转移患者的预后仍然不令人满意。为了确定骨肉瘤的新治疗靶点，我们通过cDNA微阵列分析研究了骨肉瘤的基因表达谱，发现大多数骨肉瘤样本中存在受体酪氨酸激酶样孤儿受体2（ROR 2）表达的反式激活。用针对ROR 2的siRNA处理骨肉瘤细胞系显著抑制细胞增殖和迁移。我们还鉴定了无翅型MMTV整合位点家族成员5 B（WNT 5 B）作为ROR 2的一个可能配体，并且WNT 5 B和ROR 2的生理相互作用可以增强细胞迁移，表明ROR 2和WNT 5 B在骨肉瘤细胞的转移特性中可能发挥作用。综上所述，我们的研究结果表明，WNT 5 B/ROR 2信号通路是一个有前途的骨肉瘤治疗靶点。（Cancer Sci 2009; 100：1227-1233）
Osteosarcoma is the most prevalent bone malignant tumor in children and adolescents, and displays heterogeneous histology and high propensity for distant metastasis. Although adjuvant chemotherapy remarkably improved treatment outcome over the past few decades, prognosis for osteosarcoma patients with pulmonary metastasis is still unsatisfactory. To identify novel therapeutic targets for osteosarcoma, we investigated the gene expression profile of osteosarcomas by cDNA microarray analysis and found transactivation of receptor tyrosine kinase-like orphan receptor 2 (ROR2) expression in the majority of osteosarcoma samples. Treatment of osteosarcoma cell lines with siRNA against ROR2 significantly inhibited cell proliferation and migration. We also identified wingless-type MMTV integration site family, member 5B (WNT5B) as a putative ROR2 ligand and that the physiological interaction of WNT5B and ROR2 could enhance cell migration, indicating the possible roles of ROR2 and WNT5B in the metastatic property of osteosarcoma cells. Taken together, our findings revealed that the WNT5B/ROR2 signaling pathway is a promising therapeutic target for osteosarcoma. (Cancer Sci 2009; 100: 1227-1233)