PMID- 34527741 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20210929 IS - 2314-6141 (Electronic) IS - 2314-6133 (Print) VI - 2021 DP - 2021 TI - Canine Natural Killer Cell-Derived Exosomes Exhibit Antitumor Activity in a Mouse Model of Canine Mammary Tumor. PG - 6690704 LID - 10.1155/2021/6690704 [doi] LID - 6690704 AB - Natural killer (NK) cells are key immune cells engaged in fighting infection and malignant transformation. In this study, we found that canine NK cell-derived exosomes (NK-exosomes) separated from activated cytotoxic NK cell supernatants express specific markers including CD63, CD81, Alix, HSP70, TSG101, Perforin 1, and Granzyme B. We examined the antitumor effects of NK-exosomes in an experimental murine mammary tumor model using REM134 canine mammary carcinoma cell line. We observed changes in tumor size, tumor initiation, progression, and recurrence-related markers in the control, tumor group, and NK-exosome-treated tumor group. We found that the tumor size in the NK-exosome-treated tumor group decreased compared with that of the tumor group in the REM134-driven tumorigenic mouse model. We observed significant changes including the expression of tumorigenesis-related markers, such as B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1), vascular endothelial growth factor (VEGF), matrix metallopeptidase-3 (MMP-3), interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), multidrug resistance protein (MDR), tumor suppressor protein p53 (p53), proliferating cell nuclear antigen (PCNA), and the apoptotic markers, B cell lymphoma-2 associated X (Bax) and B cell lymphoma-extra large (Bcl-xL) belonging to the Bcl-2 family, in the tumor group compared with those in the control group. The expression of CD133, a potent cancer stem cell marker, was significantly higher than that of the control. By contrast, the NK-exosome-treated tumor group exhibited a significant reduction in Bmi-1, MMP-3, IL-1beta, IL-6, TNF-alpha, Bax, Bcl-xL, and PCNA expression compared with that in the tumor group. Furthermore, the expression of CD133, which mediates tumorigenesis, was significantly decreased in the NK-exosome-treated tumor group compared with that in the tumor group. These findings indicate that canine NK-exosomes represent a promising therapeutic tool against canine solid tumors, including mammary carcinoma. CI - Copyright (c) 2021 Jienny Lee et al. FAU - Lee, Jienny AU - Lee J AUID- ORCID: 0000-0001-5192-8800 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. AD - Division of Regenerative Medicine Safety Control, Department of Chronic Disease Convergence Research, Korea National Institute of Health, Korea Disease Control and Prevention Agency, 202 Osongsaengmyeong 2-ro, Cheongju, Chungcheongbuk-do 28159, Republic of Korea. FAU - Lee, Se-A AU - Lee SA AUID- ORCID: 0000-0002-9142-7012 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. FAU - Gu, Na-Yeon AU - Gu NY AUID- ORCID: 0000-0001-6009-0093 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. FAU - Jeong, So Yeon AU - Jeong SY AUID- ORCID: 0000-0002-8006-7023 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. FAU - Byeon, Jeong Su AU - Byeon JS AUID- ORCID: 0000-0003-4977-398X AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. FAU - Jeong, Da-Un AU - Jeong DU AUID- ORCID: 0000-0002-2781-5491 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. FAU - Ouh, In-Ohk AU - Ouh IO AUID- ORCID: 0000-0001-9382-2924 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. FAU - Lee, Yoon-Hee AU - Lee YH AUID- ORCID: 0000-0003-4827-0686 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. FAU - Hyun, Bang-Hun AU - Hyun BH AUID- ORCID: 0000-0002-3429-3425 AD - Viral Disease Research Division, Animal and Plant Quarantine Agency, 177 Hyeoksin 8-ro, Gimcheon, Gyeongsangbuk-do 39660, Republic of Korea. LA - eng PT - Journal Article DEP - 20210904 PL - United States TA - Biomed Res Int JT - BioMed research international JID - 101600173 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) SB - IM MH - Animals MH - Antineoplastic Agents/pharmacology MH - Apoptosis/drug effects MH - Biomarkers, Tumor MH - Breast Neoplasms/immunology/metabolism/therapy MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Disease Models, Animal MH - Dogs MH - Exosomes/*immunology/metabolism/physiology MH - Female MH - Killer Cells, Natural/*immunology/metabolism/transplantation MH - Mammary Neoplasms, Animal/*immunology/metabolism/therapy MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Primary Cell Culture MH - Xenograft Model Antitumor Assays PMC - PMC8437631 COIS- The authors declare no conflicts of interest. EDAT- 2021/09/17 06:00 MHDA- 2021/09/30 06:00 PMCR- 2021/09/04 CRDT- 2021/09/16 07:18 PHST- 2021/01/03 00:00 [received] PHST- 2021/08/14 00:00 [accepted] PHST- 2021/09/16 07:18 [entrez] PHST- 2021/09/17 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2021/09/04 00:00 [pmc-release] AID - 10.1155/2021/6690704 [doi] PST - epublish SO - Biomed Res Int. 2021 Sep 4;2021:6690704. doi: 10.1155/2021/6690704. eCollection 2021.