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Breast Cancer Res Treat (2007) 104:267275 DOI 10.1007/s10549-006-9416-4
PRECLINICAL STUDY
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 Toi Naoki Yamamoto
Received: 17 September 2006 / Accepted: 20 September 2006 / Published online: 26 October 2006 Springer Science+Business Media B.V. 2006
Abstract 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/ccnull (NOG) mice lacking T, B and NK cells inoculated with breast cancer cells were efcient 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-b1 antibody, which transiently abrogates NK cell activity in vivo, resulted in enhanc-
ing tumor formation and organ-metastasis in comparison with non-treated NOD/SCID mice. Activated NK cells inhibited tumor growth in vivo. The rapid and efcient 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.
Keywords NOG mice NK cells Breast Cancer Immunotherapy
Electronic supplementary material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s10549-006-9416-4
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Md. Z. Dewan N. Yamamoto (&)
Department of Molecular Virology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japane-mail: [email protected]
Md. Z. Dewan N. Yamamoto AIDS Research Center, National institute of Infectious Disease, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan
H. Terunuma Biotherapy Institute of Japan, 2-4-8 Edagawa, Koutou-ku, Tokyo 135-0051,Japan
H. Terunuma H. AbeKudan Clinic, 1-9-5 Kudankita, Chiyoda-ku, Tokyo 102-0073, Japan
M. Takada M. Toi (&)
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