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Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells

Cancer Gene Therapy volume 14, pages 894–903 (2007)Cite this article

Abstract

Most advanced solid tumors metastasize to different organs. However, no gene therapy effective for multiple tumors has yet been developed. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting multiple tumors. First, we confirmed that mouse MSCs preferentially migrate to multiple tumors of the lung in the Colon-26 (C-26) lung metastasis model. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF), by an adenoviral vector with an RGD motif. MSCs expressing NK4 (NK4-MSCs) strongly inhibited development of lung metastases in the C-26 lung metastasis model after systemic administration via a tail vein. Treatment with NK4-MSCs significantly prolonged survival of the C-26-tumor-bearing mice by inhibiting tumor-associated angiogenesis and lymphangiogenesis and inducing apoptosis of the tumor cells. MSC-based gene therapy did not induce the severe adverse effects induced by conventional adenoviral vectors. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting multiple lung metastatic tumors.

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Acknowledgements

This work was supported in part by the Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, Culture, and Technology of Japan (Grant no. 17790520 and 16390232).

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Authors and Affiliations

  1. Department of Molecular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan

    M Kanehira, H Xin, K Hoshino & Y Saijo

  2. Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan

    M Kanehira, M Maemondo & T Nukiwa

  3. Laboratory of Gene Transfer and Regulation, National Institute of Biomedical Innovation, Osaka, Japan

    H Mizuguchi

  4. Pharmaceutical and Medical Agency, Tokyo, Japan

    T Hayakawa

  5. Division of Molecular Regenerative Medicine, Department of Biochemistry, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    K Matsumoto & T Nakamura

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  1. M Kanehira
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  2. H Xin
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  3. K Hoshino
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  4. M Maemondo
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Correspondence to Y Saijo.

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Kanehira, M., Xin, H., Hoshino, K. et al. Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells. Cancer Gene Ther 14, 894–903 (2007). https://doi.org/10.1038/sj.cgt.7701079

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  • DOI: https://doi.org/10.1038/sj.cgt.7701079

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