Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.
Division of Experimental Pathology, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan; Chromosomal Engineering Research Center, Tottori University, Yonago, Tottori, Japan.
Pathol Res Pract. 2022 Sep;237:154015. doi: 10.1016/j.prp.2022.154015. Epub 2022 Jul 8.
The adhesion of circulating cancer cells to vascular endothelial cells is an initial and critical step in distant metastases. Amphoterin-induced gene and open reading frame 2 (AMIGO2) was found to regulate tumor cell adhesion to hepatic endothelial cells and act as a driver gene for liver metastasis in mouse cell lines. However, whether the role of AMIGO2 observed in mouse tumor cells can be extrapolated to human cancer cells in vivo has not been verified. In this study, AMIGO2 expression in various human gastric and colorectal cancer cells was found to be closely associated with their adhesion to human hepatic sinusoidal endothelial cells (HHSECs). Constitutive AMIGO2-knockdown clones of human gastric (MKN-45) and colorectal cancer cell lines (DLD-1) were established to examine whether AMIGO2 expression in cancer cells is involved in the adhesion to HHSECs in vitro and the formation of liver metastasis in vivo. All AMIGO2-knockdown cells showed significantly attenuated adhesion to HHSECs. In vivo analysis revealed that intrasplenic inoculation of AMIGO2-knockdown clones could engraft in the spleen but significantly suppressed liver metastasis in nude mice. This study demonstrated that the role of AMIGO2 as a driver gene of liver metastasis in mouse tumor cells can be extrapolated to human cancer cells.
循环肿瘤细胞黏附血管内皮细胞是远处转移的初始和关键步骤。发现两性蛋白诱导基因和开放阅读框 2（AMIGO2）可调节肿瘤细胞与肝内皮细胞的黏附，并作为小鼠细胞系肝转移的驱动基因。然而，在小鼠肿瘤细胞中观察到的 AMIGO2 作用是否可以外推到体内的人类癌细胞尚未得到验证。在这项研究中，发现各种人胃和结直肠癌细胞中的 AMIGO2 表达与其与人肝窦内皮细胞（HHSEC）的黏附密切相关。建立了人胃癌（MKN-45）和结直肠癌细胞系（DLD-1）的稳定 AMIGO2 敲低克隆，以研究癌细胞中 AMIGO2 的表达是否参与体外黏附 HHSEC 以及体内肝转移的形成。所有 AMIGO2 敲低细胞对 HHSEC 的黏附均明显减弱。体内分析显示，AMIGO2 敲低克隆的脾内接种可在脾脏中定植，但显著抑制裸鼠的肝转移。这项研究表明，AMIGO2 作为小鼠肿瘤细胞肝转移驱动基因的作用可以外推到人类癌细胞。
