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ISSN : 2287-7991(Print)
ISSN : 2287-8009(Online)
Journal of the Preventive Veterinary Medicine Vol.45 No.3 pp.129-137

Effects of natural killer cell-derived exosomes in canine mammary tumor model

Se-A Lee1#, Na-Yeon Gu1#, So Yeon Jeong1, Seong-In Lim1, Jienny Lee1,2†, Yoon-Hee Lee1, Bang-Hun Hyun1
1Viral Disease Research Division, Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea
2Division of Regenerative Medicine Safety Control, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, Chungcheongbuk-do 28159, Republic of Korea


Natural killer (NK) cells have cytotoxic effects on tumor cells and viral pathogens. NK cell-derived exosomes (NK-exosomes) also express typical NK cell markers and cytotoxic molecules, therefore, exert anti-tumor and immune homeostatic activities. In this study, canine NK-exosomes separated from cytotoxic NK cell supernatant carried specific markers such as CD81, Alix, and Perforin 1. We examined the anti-tumor effects of NK-exosomes in an experimental murine model using the canine mammary carcinoma cells, REM134. REM134 cells were xenografted of mammary fat pad of mice. CD133, Bmi-1, MMP-3, IL-6, TNF-α, and PCNA are useful as a molecular marker for tumorigenesis and metastasis. The treatment of canine NK-exosomes inhibited tumor growth and significantly (p<0.01) downregulated the expression of Bmi-1, MMP-3, IL-6, TNF-α, and PCNA in REM134-treated mice. Also, the expression of CD133, potent cancer stem cell marker, was significantly downregulated in the canine NK-exosomes-treated mice compared with that of the tumor group. Collectively, these results suggested that canine NK-exosomes has a potential capacity for regulation of cancer progression and metastasis against canine mammary carcinoma.