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Tran et al. J Cancer Metastasis Treat 2020;6:47 Journal of Cancer
DOI: 10.20517/2394-4722.2020.104 Metastasis and Treatment

Original Article Open Access

ROR2 regulates the survival of murine
osteosarcoma cells in lung capillaries

Diem Thi Phuong Tran , Takahiro Kuchimaru , Mongkol Pongsuchart , Kha The Nguyen , John Clyde Co
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1
2
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Soriano , Tetsuya Kadonosono , Shinae Kizaka-Kondoh 1
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1 School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8501, Japan.
2 Center for Molecular Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
Correspondence to: Dr. Shinae Kizaka-Kondoh, School of Life Science and Technology, Tokyo Institute of Technology, 4259-B60
Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan. E-mail: skondoh@bio.titech.ac.jp
How to cite this article: Tran DTP, Kuchimaru T, Pongsuchart M, Nguyen KT, Co Soriano JC, Kadonosono T, Kizaka-Kondoh S.
ROR2 regulates the survival of murine osteosarcoma cells in lung capillaries. J Cancer Metastasis Treat 2020;6:47.
http://dx.doi.org/10.20517/2394-4722.2020.104

Received: 22 Sep 2020 First Decision: 10 Nov 2020 Revised: 10 Nov 2020 Accepted: 24 Nov 2020 Published: 10 Dec 2020
Academic Editor: Ian Judson Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: Lung metastasis is a leading cause of death in patients with osteosarcoma (OS). No effective therapy exists
that improves the five-year overall survival rate of OS patients with metastasis. Therefore, finding novel therapeutic
targets will help develop new treatment strategies for OS patients with lung metastasis.

Methods: Based on analysis of gene expression profiles between sublines of the Dunn OS LM8 cell line with high
(LM8-H) and low (LM8-L) metastatic ability, we have identified Wnt signal-related genes that play an important
role in lung metastasis of OS. Function of the genes was investigated by establishing sublines of gene knockout and
assessing their metastatic ability using a mouse lung metastasis model. The molecular mechanism underlying the
function of the genes was further investigated by in vitro experiments.

Results: We have identified that receptor tyrosine kinase-like orphan receptor 2 (ROR2), a receptor of the non-
canonical Wnt signaling pathway, was involved in OS cell survival in lung capillaries during metastasis. LM8-H
knocked out of Ror2 (H/Ror2-KO) significantly reduced lung metastasis by decreasing the viability in lung capillaries
48 h after intravenous injection. In vitro study revealed that ROR2 increased anoikis resistance through AKT
activation. Reconstitution of ROR2 expression in H/Ror2-KO cells restored their metastatic ability and viability in
lung capillaries.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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