Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma.
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.
Morioka
Kazuhito
K
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Tanikawa
Chizu
C
Ochi
Kensuke
K
Daigo
Yataro
Y
Katagiri
Toyomasa
T
Kawano
Hirotaka
H
Kawaguchi
Hiroshi
H
Myoui
Akira
A
Yoshikawa
Hideki
H
Naka
Norifumi
N
Araki
Nobuto
N
Kudawara
Ikuo
I
Ieguchi
Makoto
M
Nakamura
Kozo
K
Nakamura
Yusuke
Y
Matsuda
Koichi
K
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
D011956:Receptors, Cell Surface; D051153:Wnt Proteins; C078717:ROR2 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors