Breast Cancer Research and Treatment

, Volume 104, Issue 3, pp 267–275 | Cite as

Role of natural killer cells in hormone-independent rapid tumor formation and spontaneous metastasis of breast cancer cells in vivo

  • Md. Zahidunnabi Dewan
  • Hiroshi Terunuma
  • Masahiro Takada
  • Yuetsu Tanaka
  • Hiroyuki Abe
  • Tetsutaro Sata
  • Masakazu ToiEmail author
  • Naoki YamamotoEmail author
Preclinical study


Natural killer (NK) cells play a central role in host defense against tumor and virus-infected cells. Direct role of NK cells in tumor growth and metastasis remains to be elucidated. We here demonstrated that NOD/SCID/γcnull (NOG) mice lacking T, B and NK cells inoculated with breast cancer cells were efficient in the formation of a large tumor and spontaneous organ-metastasis. In contrast, breast cancer cells produced a small tumor at inoculated site in T and B cell knock-out NOD/SCID mice with NK cells while completely failed to metastasize into various organs. Immunosupression of NOD/SCID by treatment with an anti-murine TM-β1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhancing tumor formation and organ-metastasis in comparison with non-treated NOD/SCID mice. Activated NK cells inhibited tumor growth in vivo. The rapid and efficient engraftment of the breast cancer cells in NOG mice suggests that this new animal model could provide a unique opportunity to understand and investigate the mechanism of tumor cell growth and metastasis. Our results suggest that NK cells play an important role in cancer growth and metastasis and could be a promising immunotherapeutic strategy against cancer either alone or in combination with conventional therapy.


NOG mice NK cells Breast Cancer Immunotherapy 



We thank K. Ohba of Department of Molecular Virology, S. Ichinose of Instrumental Analysis Research Center and S. Endo of Animal Research Center, Tokyo Medical and Dental University for their advice and assistance with the experiments. We also thank Y. Sato of the National Institute of Infectious Diseases for her excellent technical assistance. This work was supported by grants from the Ministry of Education, Science and Culture; the Ministry of Health, Labor and Welfare; and Human Health Science of Japan.

Supplementary material


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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Md. Zahidunnabi Dewan
    • 1
    • 2
  • Hiroshi Terunuma
    • 3
    • 4
  • Masahiro Takada
    • 5
  • Yuetsu Tanaka
    • 6
  • Hiroyuki Abe
    • 4
  • Tetsutaro Sata
    • 7
  • Masakazu Toi
    • 5
    Email author
  • Naoki Yamamoto
    • 1
    • 2
    Email author
  1. 1.Department of Molecular Virology, Graduate SchoolTokyo Medical and Dental UniversityTokyoJapan
  2. 2.AIDS Research CenterNational institute of Infectious DiseaseTokyoJapan
  3. 3.Biotherapy Institute of JapanTokyoJapan
  4. 4.Kudan ClinicTokyoJapan
  5. 5.Division of Clinical Trials and Research, Breast Cancer Research and Treatment ProgramTokyo Metropolitan Komagome Hospital, Tokyo Medical Center for Cancer and Infectious DiseaseTokyoJapan
  6. 6.Department of Infectious Disease and Immunology, Faculty of MedicineUniversity of the RyukyusOkinawaJapan
  7. 7.Department of PathologyNational Institute of Infectious DiseasesTokyoJapan

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