Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma

• Published in: Cancer science 2009-07, Vol.100 (7), p.1227-1233
• Main Authors: Morioka, Kazuhito, Tanikawa, Chizu, Ochi, Kensuke, Daigo, Yataro, Katagiri, Toyomasa, Kawano, Hirotaka, Kawaguchi, Hiroshi, Myoui, Akira, Yoshikawa, Hideki, Naka, Norifumi, Araki, Nobuto, Kudawara, Ikuo, Ieguchi, Makoto, Nakamura, Kozo, Nakamura, Yusuke, Matsuda, Koichi
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bone Neoplasms - drug therapy; Bone Neoplasms - enzymology; Cell Line; Cell Line, Tumor; Chlorocebus aethiops; COS Cells; Diseases of the osteoarticular system; Humans; Medical sciences; Mice; Mouse mammary tumor virus; NIH 3T3 Cells; Original; Osteosarcoma - drug therapy; Osteosarcoma - enzymology; Receptor Protein-Tyrosine Kinases - antagonists & inhibitors; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptor Tyrosine Kinase-like Orphan Receptors; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Signal Transduction; Tumors; Tumors of striated muscle and skeleton; Wnt Proteins - genetics; Wnt Proteins - metabolism
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/j.1349-7006.2009.01165.x

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)