Tanio Akimitsu, Saito Hiroaki, Amisaki Masataka, Hara Kazushi, Sugezawa Ken, Uejima Chihiro, Tada Yoichiro, Kihara Kyoichi, Yamamoto Manabu, Nosaka Kanae, Sasaki Ryo, Osaki Mitsuhiko, Okada Futoshi, Fujiwara Yoshiyuki
Division of Gastrointestinal and Pediatric Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan.
Department of Surgery, Japanese Red Cross Tottori Hospital, Yonago, Tottori 680-8517, Japan.
Oncol Lett. 2021 Apr;21(4):278. doi: 10.3892/ol.2021.12539. Epub 2021 Feb 10.
Our previous study showed that adhesion molecule with immunoglobulin like domain 2 (AMIGO2) is a pivotal driver gene of liver metastasis via regulating tumor cell adhesion to liver endothelial cells in mouse models. The aim of the present study was to clarify the role of AMIGO2 in liver metastasis in patients the colorectal cancer (CRC). Two human CRC cell lines, Caco-2 (AMIGO2-low) and HCT116 (AMIGO2-high), were used in this study. AMIGO2-overexpressing Caco-2 and AMIGO2-knockdown HCT116 cells were generated by transfection with an AMIGO2 expression vector or AMIGO2 small interfering RNA, respectively. Cell proliferation, invasion and adhesion to human liver endothelial cells were examined in studies. Immunohistochemical analysis was also performed to evaluate the association between AMIGO2 expression and liver metastasis in patients with CRC. studies revealed that cell proliferation, invasion and adhesion to liver endothelial cells were accelerated by upregulation of AMIGO2 expression, but suppressed by downregulation of AMIGO2 expression in human CRC cells. Immunohistochemical analysis using clinical CRC specimens revealed that AMIGO2 expression was associated with the frequency of liver metastasis (P<0.01), but not that of pulmonary metastasis (P=0.611) and peritoneal dissemination (P=0.909). In addition, AMIGO2 expression levels in tumor cells were significantly higher in liver metastatic foci than primary lesions (P=0.012). In conclusion, the present results indicated that AMIGO2 expression may contribute to the formation of liver metastasis in CRC.
我们之前的研究表明，具有免疫球蛋白样结构域2的黏附分子（AMIGO2）在小鼠模型中通过调节肿瘤细胞与肝内皮细胞的黏附，是肝转移的关键驱动基因。本研究的目的是阐明AMIGO2在结直肠癌（CRC）患者肝转移中的作用。本研究使用了两种人CRC细胞系，Caco-2（AMIGO2低表达）和HCT116（AMIGO2高表达）。分别通过用AMIGO2表达载体或AMIGO2小干扰RNA转染，构建了AMIGO2过表达的Caco-2细胞和AMIGO2敲低的HCT116细胞。在研究中检测了细胞增殖、侵袭以及与人肝内皮细胞的黏附情况。还进行了免疫组织化学分析，以评估AMIGO2表达与CRC患者肝转移之间的关联。研究表明，在人CRC细胞中，AMIGO2表达上调可加速细胞增殖、侵袭以及与肝内皮细胞的黏附，而AMIGO2表达下调则会抑制这些过程。使用临床CRC标本进行的免疫组织化学分析显示，AMIGO2表达与肝转移频率相关（P<0.01），但与肺转移频率（P=0.611）和腹膜播散频率（P=0.909）无关。此外，肝转移灶中肿瘤细胞的AMIGO2表达水平明显高于原发灶（P=0.012）。总之，目前的结果表明，AMIGO2表达可能有助于CRC肝转移的形成。
