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

M. Kanehira, H. Xin, K. Hoshino, M. Maemondo, H. Mizuguchi, T. Hayakawa, K. Matsumoto, T. Nakamura, T. Nukiwa, Y. Saijo

Research output: Contribution to journalArticle

119 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)894-903
Number of pages10
JournalCancer Gene Therapy
Volume14
Issue number11
DOIs
Publication statusPublished - 2007 Nov

Keywords

  • Lung metastases
  • Mesenchymal stem cell
  • Multiple tumors

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells'. Together they form a unique fingerprint.

  • Cite this

    Kanehira, M., Xin, H., Hoshino, K., Maemondo, M., Mizuguchi, H., Hayakawa, T., Matsumoto, K., Nakamura, T., Nukiwa, T., & Saijo, Y. (2007). Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells. Cancer Gene Therapy, 14(11), 894-903. https://doi.org/10.1038/sj.cgt.7701079