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The involvement of NK cell activation following intranasal administration of CpG DNA lipoplex in the prevention of pulmonary metastasis and peritoneal dissemination in mice

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Abstract

Synthetic oligodeoxynucleotides containing CpG motifs (CpG DNA) can activate immunocompetent cells, which may possess antitumor activity. Previously, we found that when the cationic liposomes complexes formed with CpG DNA (CpG DNA lipoplex) were administered intranasally, they could prevent pulmonary metastasis in mice. However, the mechanisms underlying this process are unknown. In the present study, we show that natural killer (NK) cells play an important role in preventing pulmonary metastasis and peritoneal dissemination in a mouse model of metastatic disease. Further, in vitro, the NK cells obtained from mice treated with CpG DNA lipoplex showed higher cytotoxicity compared with untreated mice and in vivo, depletion of NK cells (achieved through injection of rabbit anti-asialo GM1 serum), abolished the inhibitory effect of CpG DNA lipoplex on pulmonary metastasis and peritoneal dissemination. In contrast, macrophage elimination did not disrupt the effects of the CpG DNA lipoplex. These results suggest that intranasal administration of CpG DNA lipoplex could prevent pulmonary metastasis and peritoneal dissemination by activating NK cells.

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Abbreviations

CpG DNA:

Synthetic oligodeoxynucleotides containing CpG motifs

CpG DNA lipoplex:

CpG DNA complexed with cationic liposome

DOTMA:

N-[1-(2,3-dioleyloxy) propyl]-N,N,N-trimethylammonium chloride

i.p.:

Intraperitoneal

NK cells:

Natural killer cells

NT:

Not treated

γ-C4:

γ-Carrageenan type IV

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Scientific Research (A) (23240072) and by a fellowship grant from the Japan Society for the Promotion of Sciences (23·2743).

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Correspondence to Mitsuru Hashida.

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Zhou, S., Kawakami, S., Higuchi, Y. et al. The involvement of NK cell activation following intranasal administration of CpG DNA lipoplex in the prevention of pulmonary metastasis and peritoneal dissemination in mice. Clin Exp Metastasis 29, 63–70 (2012). https://doi.org/10.1007/s10585-011-9429-1

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  • DOI: https://doi.org/10.1007/s10585-011-9429-1

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