Lee Kyung-Mi, An Ju-Hyun, Yang Se-Jin, Park Su-Min, Lee Jeong-Hwa, Chae Hyung-Kyu, Song Woo-Jin, Youn Hwa-Young
Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Science, College of Veterinary Medicine, Seoul National University, Seoul, Republic of Korea.
Department of Veterinary Internal Medicine, College of Veterinary Medicine and Research Institute of Veterinary Science, Jeju National University, Jeju, Republic of Korea
Anticancer Res. 2021 Feb;41(2):719-730. doi: 10.21873/anticanres.14823.
BACKGROUND/AIM: The purpose of this study was to evaluate the effect of extracellular vesicles derived from canine M1-polarized macrophages (M1EVs) on canine tumor cells, such as D17 (osteosarcoma cells) and LMeC (melanoma cells).
Protein expression was determined by western blot analysis. Gene expression was determined by RT-qPCR. In addition, cell apoptosis was analyzed by Annexin V/PI staining.
In the case of M1EV, the levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-1β were increased, and nitrate/nitrite levels were also increased. M1EV induced apoptosis of tumor cells by increasing caspase-3 and caspase-7 activation. In addition, M1EVs decreased expression of CCR4, Foxp3 and CTLA-4 in canine peripheral mononuclear cells cocultured with tumor cells.
M1EV could be an effective anti-cancer therapeutic approach in melanoma and osteosarcoma and M1EVs can be used as immunomodulators in the tumor microenvironment for cancer treatment.
背景/目的：本研究旨在评估犬M1极化巨噬细胞来源的细胞外囊泡（M1EVs）对犬肿瘤细胞（如D17骨肉瘤细胞和LMeC黑色素瘤细胞）的影响。
通过蛋白质印迹分析确定蛋白质表达。通过RT-qPCR确定基因表达。此外，通过Annexin V/PI染色分析细胞凋亡。
在M1EV的情况下，TNF-α、IL-6和IL-1β等促炎细胞因子水平升高，硝酸盐/亚硝酸盐水平也升高。M1EV通过增加caspase-3和caspase-7的激活诱导肿瘤细胞凋亡。此外，M1EVs降低了与肿瘤细胞共培养的犬外周血单个核细胞中CCR4、Foxp3和CTLA-4的表达。
M1EV可能是黑色素瘤和骨肉瘤的一种有效的抗癌治疗方法，并且M1EVs可作为肿瘤微环境中的免疫调节剂用于癌症治疗。
