Open AccessOrphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma
Author(s) -
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
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01165.x
Subject(s) - osteosarcoma , cancer research , transactivation , metastasis , receptor tyrosine kinase , medicine , tyrosine kinase , orphan receptor , biology , pathology , receptor , cancer , gene , gene expression , transcription factor , genetics
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)