title: Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma.
abstract: 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.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Morioka
authors.forename: Chizu
authors.initials: C
authors.lastname: Tanikawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ochi
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Kawano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Myoui
authors.forename: Hideki
authors.initials: H
authors.lastname: Yoshikawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Naka
authors.forename: Nobuto
authors.initials: N
authors.lastname: Araki
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kudawara
authors.forename: Makoto
authors.initials: M
authors.lastname: Ieguchi
authors.forename: Kozo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D012516:Osteosarcoma / Q000188:drug therapy / Q000201:enzymology*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D011956:Receptors, Cell Surface; D051153:Wnt Proteins; C078717:ROR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors