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Biological properties and gene expression associated with metastatic potential of human osteosarcoma

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Abstract

Lung metastasis has a great influence on the prognosis of patients with osteosarcoma. We previously established two high-metastatic sublines, M112 and M132, from the HuO9 human osteosarcoma cell line by in vivo selection. In this study, we newly isolated a high-metastatic subline, H3, and three low-metastatic sublines, L6, L12 and L13, from HuO9 by the dilution plating method. Three high-metastatic sublines produced more than 200 metastatic nodules in the lung, while three low-metastatic sublines produced no or few nodules after injection of 2 × 106 cells into the tail vein of nude mice. There were significant differences in the motility and invasiveness between high- and low-metastatic sublines, whereas the growth rates in vitro and the tumorigenicity in vivo showed no correlation with their metastatic abilities. Early adherence to culture plates was significantly lower in two of three low-metastatic sublines, which occupied smaller surface areas on the culture plates than other sublines did. Comparison of the expression of 637 cancer-related genes by cDNA microarray revealed that seven genes were differentially expressed between high- and low-metastatic sublines. Among them, five genes (AXL, TGFA, COLL7A1, WNT5A, and MKK6) were associated with adherence, motility, and/or invasiveness. These results suggest that the differences in motility/invasiveness and adhesive abilities are key determinants of lung metastasis in osteosarcoma.

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Authors and Affiliations

  1. Division of Biology, National Cancer Center Research Institute, Tokyo, Japan

    Tetsuhiro Nakano, Masachika Tani, Yasunori Ishibashi, Kenji Kimura, Yong-Bum Park, Natsuko Imaizumi & Jun Yokota

  2. Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan

    Hiroyuki Tsuda

  3. Genetics Divisions, National Cancer Center Research Institute, Tokyo, Japan

    Kazuhiko Aoyagi & Hiroki Sasaki

  4. Second Department of Surgery, Gunma University, Gunma, Japan

    Susumu Ohwada

Authors
  1. Tetsuhiro Nakano
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  2. Masachika Tani
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  11. Jun Yokota
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Correspondence to Jun Yokota.

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Nakano, T., Tani, M., Ishibashi, Y. et al. Biological properties and gene expression associated with metastatic potential of human osteosarcoma. Clin Exp Metastasis 20, 665–674 (2003). https://doi.org/10.1023/A:1027355610603

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