Low-dose eribulin reduces lung metastasis of osteosarcoma in vitro and in vivo
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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
Yoshihiro Yui, email: firstname.lastname@example.org
Keywords: eribulin; osteosarcoma; metastasis; LM8; circulating tumor cells
Received: September 07, 2018 Accepted: December 20, 2018 Published: January 04, 2019
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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