Korea Radioisotope Center for Phamaceuticals, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Korea.
BK21 Plus, Department of Cellular and Molecular Medicine, Konkuk University School of Medicine, Seoul 05029, Korea.
Int J Mol Sci. 2021 Jul 13;22(14):7478. doi: 10.3390/ijms22147478.
This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer.
An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting.
In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C) for monocytes, M1-tumour phenotypes from TAMs, and F4/80 for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C and major histocompatibility complex class II for M1-tumour phenotypes from TAMs on F4/80 from the tumour tissue in the study group had significantly higher values compared with the control group.
The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.
本研究旨在探讨簇分化(CD)39 和 CD73 抑制剂对结肠癌小鼠肿瘤相关巨噬细胞(TAMs)、M1 与 M2 肿瘤表型表达的影响。
进行了结肠癌细胞与来自小鼠骨髓(BM)的免疫细胞的体内共培养研究。在证实多金属氧酸盐(POM-1)作为 CD39 抑制剂对 TAMs 的作用后,将小鼠皮下注射 CT26 细胞后分别随机分为对照组(无 POM-1)和研究组(有 POM-1)。注射后 14 天,处死小鼠,采用荧光激活细胞分选术评估 TAMs。
在体内研究中,与 POM-1 共培养显著增加了 CT26 细胞的凋亡。与 POM-1 共培养的细胞群体中,髓样细胞的 CD11b、单核细胞的淋巴细胞抗原 6 复合物、座 C(Ly6C)、TAMs 的 M1 肿瘤表型和巨噬细胞的 F4/80 表达均显著增加。在体内研究中,与对照组(无 POM-1)相比,研究组(有 POM-1)的肿瘤生长明显受到限制。与对照组相比,研究组肿瘤组织中 TAMs 的 Ly6C 和主要组织相容性复合体 II 表达的 M1 肿瘤表型明显更高。
POM-1 抑制 CD39 可防止结肠癌小鼠的生长,这与肿瘤组织中 TAMs 的 M1 肿瘤表型表达增加有关。