Inhibition of tumor growth and invasion by a four-kringle antagonist (HGF/NK4) for hepatocyte growth factor (original) (raw)

Oncogene volume 17, pages 3045–3054 (1998)Cite this article

Abstract

Invasion of various carcinoma cells follows their interaction with stromal cells. Hepatocyte growth factor (HGF), four-kringle-containing growth factor, is a mesenchymal or stromal-derived mediator which affects the growth and the invasiveness of carcinoma cells. We now have evidence that a four-kringle-containing antagonist for HGF, HGF/NK4 inhibits invasion of tumors in vivo, as well as in vitro. HGF/NK4 competitively inhibited the binding of HGF to Met/HGF receptors on GB-d1 human gallbladder carcinoma cells. HGF induced invasion of the cells through Matrigel basement membrane components and into collagen gels, but HGF-induced invasion was inhibited by HGF/NK4. Invasion of GB-d1 cells was induced by co-cultivation with stromal fibroblasts, which mimics tumor-stromal interaction, but it was almost completely suppressed by HGF/NK4. Likewise, invasive growth induced by HGF in collagen gels in GB-d1 cells, HuCC-T1 human cholangiocarcinoma cells, and ME-180 human uterus cervical carcinoma cells was also strongly inhibited by HGF/NK4. When GB-d1 cells were implanted subcutaneously into nude mouse, tumor cells invaded muscular tissue, but the infusion of HGF/NK4 inhibited this invasion. Furthermore, HGF/NK4 increased apoptotic cell death of GB-d1 cells and inhibited tumor growth in vivo. These results indicate that HGF/NK4 may inhibit growth and invasion of carcinoma cells, as mediated by HGF during tumor-stromal interactions. We propose that there is a unique therapeutic potential for HGF/NK4 to prevent tumor invasion and perhaps even metastasis.

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Authors and Affiliations

  1. Division of Biochemistry, Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, 565-0871, Osaka, Japan
    Kazuhiko Date, Kunio Matsumoto, Keiji Kuba & Toshikazu Nakamura
  2. Department of Surgery 1, Kyushu University Faculty of Medicine, Maidashi, 812-0054, Fukuoka, Japan
    Hideo Shimura & Masao Tanaka

Authors

  1. Kazuhiko Date
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  2. Kunio Matsumoto
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  3. Keiji Kuba
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  4. Hideo Shimura
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  5. Masao Tanaka
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  6. Toshikazu Nakamura
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Date, K., Matsumoto, K., Kuba, K. et al. Inhibition of tumor growth and invasion by a four-kringle antagonist (HGF/NK4) for hepatocyte growth factor.Oncogene 17, 3045–3054 (1998). https://doi.org/10.1038/sj.onc.1202231

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