Oncotarget

Research Papers:

Low-dose eribulin reduces lung metastasis of osteosarcoma in vitro and in vivo

Kenta Watanabe _, Yoshihiro Yui, Satoru Sasagawa, Kayo Suzuki, Masahiko Kanamori, Taketoshi Yasuda and Tomoatsu Kimura

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Abstract

Kenta Watanabe1,2,*, Yoshihiro Yui2,*, Satoru Sasagawa2, Kayo Suzuki1, Masahiko Kanamori3, Taketoshi Yasuda1 and Tomoatsu Kimura1

1Department of Orthopedic Surgery, University of Toyama, Toyama, Japan

2Research Institute, Nozaki Tokushukai Hospital, Osaka, Japan

3Department of Human Science, University of Toyama, Toyama, Japan

*These authors contributed equally to this work

Correspondence to:

Yoshihiro Yui, email: yoshihiro.yui@tokushukai.jp

Keywords: eribulin; osteosarcoma; metastasis; LM8; circulating tumor cells

Received: September 07, 2018     Accepted: December 20, 2018     Published: January 04, 2019

ABSTRACT

Lung metastasis markedly reduces the prognosis of osteosarcoma. Moreover, there is no effective treatment for lung metastasis, and a new treatment strategy for the treatment of osteosarcoma lung metastasis is required. Therefore, in this study, we investigated the suppressive effect of the microtubule inhibitor eribulin mesylate (eribulin) on lung metastasis of osteosarcoma. At concentrations >proliferation IC50, eribulin induced cell cycle arrest and apoptosis in a metastatic osteosarcoma cell line, LM8. However, at concentrations <proliferation IC50, (low dose), eribulin changed cell morphology and decreased LM8 migration. Low eribulin concentrations also reduced directionality during migration, peripheral localization of adenomatous polyposis coli protein, and turnover of focal adhesions. In a three-dimensional collagen culture system, low eribulin concentrations inhibited tumor cell proliferation and colony formation. Higher doses of eribulin administered on a standard schedule inhibited lung metastasis and primary tumor growth in a murine osteosarcoma metastasis model. Frequent low-dose eribulin administration (0.3 mg/kg every 4 days × 4) effectively inhibited lung metastasis but had little effect on primary tumor growth. Overall, our results indicate that eribulin could reduce osteosarcoma lung metastasis.


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