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Title of Journal: Breast Cancer Res Treat

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Abbravation: Breast Cancer Research and Treatment

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Springer US

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DOI

10.1007/978-981-10-0875-7_3

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ISSN

1573-7217

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Mechanistic analysis of the antitumor efficacy of

Authors: Keiko Kajitani Yuka Tanaka Koji Arihiro Tsuyoshi Kataoka Hideki Ohdan
Publish Date: 2012/01/20
Volume: 134, Issue: 1, Pages: 139-155
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Abstract

We investigated the role of human natural killer NK cells in the peripheral blood PB and liver in controlling breast cancer The proportion of NK cells among liver mononuclear cells was significantly higher than among PB mononuclear cells Liver NK cells inductively expressed higher levels of tumor necrosis factorrelated apoptosisinducing ligand TRAIL than PB NK cells in response to interleukin2 IL2 Liver NK cells displayed higher cytotoxicity against various breast cancer cell lines MDAMB231 MDAMB453 MDAMB468 and MCF7 after IL2 stimulation than did PB NK cells AntiHER2 monoclonal antibody mAb promoted the cytotoxicity of both the types of NK cells toward HER2expressing cell lines All breast cancer cell lines highly expressed deathinducing TRAIL receptors death receptor 4 but did not express deathinhibitory receptors DcR1 and DcR2 Both PB and liver NK cellinduced cytotoxicity was inhibited partially by antiTRAIL mAb and more profoundly by the combination of antiTRAIL mAb and concanamycin A indicating that TRAIL and perforin are involved IL2stimulated liver and PB NK cells exhibited upregulated expression of CXCR3 which bind to the chemokines CXCL9 CXCL10 and CXCL11 secreted by breast cancer cells We also found that IFNγ promoted the production of CXCL10 from breast cancer cells The results of this study show that IFNγ secreted from NK cells likely promotes the production of CXCL10 from breast cancer cells which in turn accelerates the migration of CXCR3expressing NK cells into the tumor site These findings suggest the possibility of a therapeutic approach by either activation of endogenous PB and liver NK cells or adoptive transfer of in vitroactivated autologous NK cellsWe thank Drs Kohei Ishiyama and Masahiro Ohira for their advice and encouragement and Drs Doskali Marlen Yuka Igarashi and Nabin Basnet and Ms Yuko Ishida and Ms Midori Kiyokawa for their expert technical assistance This work was supported by a GrantinAid for Scientific Research A from the Japan Society for the Promotion of Science and a GrantinAid for the Research on Hepatitis and BSE from the Japanese Ministry of Health Labour and Welfare

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  6. Biopsy sampling of breast lesions: comparison of core needle- and vacuum-assisted breast biopsies
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  13. Comprehensive analysis of oncogenic effects of PIK3CA mutations in human mammary epithelial cells
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