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Virology

Rapid tumor formation and development of neutrophilia and splenomegaly in nude mice transplanted with human cells expressing human T cell leukemia virus type I or Tax1

Leukemia volume 14, pages 1467–1476 (2000)Cite this article

Abstract

Human T cell leukemia virus type I (HTLV-I) or its transcriptional trans-activator, Tax1, was introduced into a human osteosarcoma cell line, HOS, and a Moloney murine sarcoma virus-positive HOS cell line, S+L−HOS. These HTLV-I- or Tax1-expressing cells were injected subcutaneously into nude mice to investigate the effects of HTLV-I on their tumorigenicities. HOS cells did not form any tumors even in the presence of HTLV-I or Tax1. S+L−HOS cells did form small tumors in two-thirds of nude mice. Infection of S+L−HOS cells with HTLV-I, or transduction of Tax1 into S+L−HOS cells markedly facilitated the tumor formation, and the tumor-bearing mice showed marked splenomegaly and neutrophilia. Elevated levels of granulocyte colony-stimulating factor (G-CSF) were detected in sera of these mice and also in the culture supernatants of Tax1-expressing human cells, suggesting that G-CSF in the mouse sera was produced by the human cells. In sera of some mice with splenomegaly and neutrophilia, high levels of murine granulocyte–macrophage colony-stimulating factor (mGM-CSF) were observed, suggesting that Tax1 produced by human cells induced mouse cells to produce mGM-CSF. Only S+L−HOS cell lines expressing Tax1 showed high tumorigenicity in nude mice. Thus, this system will be a useful model of tumor formation, splenomegaly and neutrophilia dependent on Tax1.

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Acknowledgements

The authors thank Drs J Hirato and Y Nakazato (Gunma University) for suggestion in histopathological analyses and T Nakamura (Gunma University) for technical support. We are grateful to Drs A Yuo, A Togawa (International Medical Center of Japan) and M Uchida (Jichi Medical College) for suggestions on the colony formation assay. We also thank Kirin Brewery Co for kindly supplying cytokines. This work was supported in part by grants-in-aid from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan.

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  1. Y Soda

    Present address: Division of Molecular Therapy, Advanced Clinical Research Center, Institute of Medical Sciences, University of Tokyo, Tokyo

  2. K Shimotohno

    Present address: Institute for Virus Research, Kyoto University, Kyoto, Japan

Authors and Affiliations

  1. Department of Virology and Preventive Medicine, Gunma University School of Medicine, Gunma, Japan

    Y Soda, A Jinno & H Hoshino

  2. Department of Immunology, School of Hygienic Sciences, Kitasato University, Kanagawa, Japan

    Y Tanaka & T Akagi

  3. Virology Division, National Cancer Center Research Institute, Tokyo, Japan

    K Shimotohno

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Soda, Y., Jinno, A., Tanaka, Y. et al. Rapid tumor formation and development of neutrophilia and splenomegaly in nude mice transplanted with human cells expressing human T cell leukemia virus type I or Tax1. Leukemia 14, 1467–1476 (2000). https://doi.org/10.1038/sj.leu.2401844

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