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PMID:19486338

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Citation

Morioka, K, Tanikawa, C, Ochi, K, Daigo, Y, Katagiri, T, Kawano, H, Kawaguchi, H, Myoui, A, Yoshikawa, H, Naka, N, Araki, N, Kudawara, I, Ieguchi, M, Nakamura, K, Nakamura, Y and Matsuda, K (2009) Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma. Cancer Sci. 100:1227-33

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.

Links

PubMed Online version:10.1111/j.1349-7006.2009.01165.x

Keywords

Animals; Bone Neoplasms/drug therapy; Bone Neoplasms/enzymology; COS Cells; Cell Line; Cell Line, Tumor; Cercopithecus aethiops; Humans; Mice; NIH 3T3 Cells; 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; Wnt Proteins/genetics; Wnt Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ROR2

involved_in

GO:0030335: positive regulation of cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ROR2

involved_in

GO:0008285: negative regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ROR2

enables

GO:0017147: Wnt-protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9H1J7

F

Seeded From UniProt

complete

HUMAN:WNT5B

enables

GO:0005102: signaling receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q01974

F

Seeded From UniProt

complete

HUMAN:WNT5B

involved_in

GO:0030335: positive regulation of cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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