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Establishment and characterization of a new highly metastatic human osteosarcoma cell line

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Abstract

Osteosarcoma is the most common primary malignancy of bone in children and young adults. There is a paucity of tumorigenic and highly metastatic human osteosarcoma cell lines that have not been further transformed by exogenous means. Here we establish and characterize a highly metastatic human osteosarcoma cell line that is derived from a poorly metastatic MG63 line through serial passage in nude mice via intratibial injections. The occasional pulmonary metastases developed from MG63 were harvested and repassaged in mice until a highly metastatic subline (MG63.2) was established. The parental MG63 and highly metastatic MG63.2 cells were further characterized in vitro and in vivo. MG63.2 cells demonstrated increased cell migration and invasion compared to the parental MG63 cells. Conversely, cell adhesion was significantly greater in MG63 cells when compared to the MG63.2 cells. MG63.2 cells grew at a slightly slower rate than that of the parental cells. When injected into nude mice, MG63.2 cells had a greater than 200-fold increase in developing pulmonary metastases compared to the parental MG63 cells. MG63.2 cells also formed larger primary tumors when compared to the parental MG63 cells. Further analysis revealed that ezrin expression was up-regulated in the metastatic MG63.2 cells. Interestingly, expressions of MMP-2 and MMP-9 were down-regulated, and expression of TIMP-2 was up-regulated in the MG63.2 cells. Taken together, we have established and characterized a highly metastatic human osteosarcoma cell line that should serve as a valuable tool for future investigations on the pathogenesis, metastasis, and potential treatments of human osteosarcoma.

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Acknowledgments

This work was funded by the Orthopaedic Research and Education Foundation (HHL, TCH and RCH), the Brinson Foundation (HHL, TCH and RCH), the American Cancer Society (HHL and TCH), and the National Institute of Health (HHL, TCH and RCH). We would like to thank Dr. Ernst Lengyel for providing the MMP-2, MMP-9, TIMP-1, and TIMP-2 antibodies.

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Authors and Affiliations

  1. The Children’s Hospital and Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education of China, Chongqing Medical University, 400016, Chongqing, China

    Yuxi Su, Xiaoji Luo, Bai-Cheng He, Yi Wang, Liang Chen, Guo-Wei Zuo, Bo Liu, Yang Bi, Jiayi Huang, Gao-Hui Zhu, Yun He, Quan Kang, Jinyong Luo, Jin Chen, Xianqing Jin & Tong-Chuan He

  2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC3079, Chicago, IL, 60637, USA

    Yuxi Su, Xiaoji Luo, Bai-Cheng He, Yi Wang, Liang Chen, Guo-Wei Zuo, Bo Liu, Yang Bi, Jiayi Huang, Gao-Hui Zhu, Yun He, Quan Kang, Jinyong Luo, Jikun Shen, Jin Chen, Rex C. Haydon, Tong-Chuan He & Hue H. Luu

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  1. Yuxi Su
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Correspondence to Hue H. Luu.

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Su, Y., Luo, X., He, BC. et al. Establishment and characterization of a new highly metastatic human osteosarcoma cell line. Clin Exp Metastasis 26, 599–610 (2009). https://doi.org/10.1007/s10585-009-9259-6

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