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Establishment of human osteosarcoma cell lines with high metastatic potential to lungs and their utilities for therapeutic studies on metastatic osteosarcoma
Authors:Kimura Kenji  Nakano Tetsuhiro  Park Yong-Bum  Tani Masachika  Tsuda Hiroyuki  Beppu Yasuo  Moriya Hideshige  Yokota Jun
Affiliation:(1) Biology and Chemotherapy Divisions, National Cancer Center Research Institute, Tokyo 104-0045, Japan;(2) Department of Orthopedic Surgery, Chiba University, Chiba 260-8677, Japan;(3) Experimental Pathology and Chemotherapy Divisions, National Cancer Center Research Institute, Tokyo 104-0045, Japan;(4) Orthopedic Division, National Cancer Center Hospital, Tokyo 104-0045, Japan;(5) Biology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan
Abstract:Relevant animal models for metastasis of osteosarcoma is needed to understand the biology and to develop the treatment modality of metastasis of human osteosarcoma. Therefore, we screened six human osteosarcoma cell lines for metastatic ability in nude mice. The HuO9 cell line was identified as being metastatic to the lung after intravenous injection. We established two sublines, HuO9-M112 and HuO9-M132, with high metastatic potential to the lung from the parental HuO9 cells by in vivo selection. There were no differences between these two sublines and the parental cells in the growth rate in vitro and the tumorigenicity after subcutaneous injection in nude mice, however, mice injected with the metastatic sublines became moribund earlier than mice injected with the parental HuO9 cells did. Thus, adriamycin (ADR) and recombinant interleukin-12 (IL-12) were administered to mice injected with the HuO9-M112 subline to suppress experimental lung metastases. Production of lung colonies was significantly suppressed and the prognoses of mice were significantly improved by both ADR and IL-12 treatments. These results indicate that both ADR and IL-12 are effective agents against pulmonary metastatic osteosarcoma, and that these sublines are useful for studies on the biological behavior and treatment of pulmonary metastatic osteosarcoma. This revised version was published online in July 2006 with corrections to the Cover Date.
Keywords:adriamycin  human osteosarcoma cell line   in vivo selection  interleukin-12 lung metastasis
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