Department of General Surgery, Shengzhou People's Hospital, Branch of First Affiliated Hospital of Zhejiang University, Shengzhou, Zhejiang, China (mainland).
Med Sci Monit. 2019 Feb 24;25:1469-1479. doi: 10.12659/MSM.911944.
BACKGROUND Intrahepatic and distant metastases could be the major cause of treatment failure in hepatocellular carcinoma (HCC). The deep mechanism of HCC metastasis is closely related to the interaction between integrins and extracellular matrix (ECM) in tumor microenvironment. MATERIAL AND METHODS In vitro cell adhesion assay was performed to determine the capability of adhering to ECM elements of HCC cells. To modulate the expression status of ADAR1 p110 in tumor cells, lentivirus system was applied. Meanwhile, patients' HCC samples and orthotopic xenograft mouse model were used for verifying our in vitro data. RESULTS ADAR1 p110 could strongly enhance the adhesion of HCC tumor cells to ECM, which was usually regarded as the initiation of tumor invasion. Such phenotype was caused due to up-regulation of ITGA2 both in mRNA and protein level. Moreover, specimen collected from HCC patients revealed a positive correlation between ADAR1 and ITGA2. Finally, ADAR1 p110 promoted HCC metastasis was verified when we applied orthotopic xenograft mouse model. CONCLUSIONS ADAR1 could enhance HCC metastasis by promoting tumor cells adhering to ECM via increasing ITGA2 expression. This phenomenon could provide novel information to better understanding the mechanism of HCC metastasis procedure.
肝内和远处转移可能是肝细胞癌 (HCC) 治疗失败的主要原因。HCC 转移的深层机制与肿瘤微环境中整合素与细胞外基质 (ECM) 之间的相互作用密切相关。
通过体外细胞黏附实验来确定 HCC 细胞黏附 ECM 成分的能力。为了调节肿瘤细胞中 ADAR1 p110 的表达状态，应用了慢病毒系统。同时，使用患者的 HCC 样本和原位异种移植小鼠模型来验证我们的体外数据。
ADAR1 p110 可显著增强 HCC 肿瘤细胞与 ECM 的黏附能力，这通常被认为是肿瘤侵袭的开始。这种表型是由于 ITGA2 在 mRNA 和蛋白水平的上调所致。此外，从 HCC 患者中采集的标本显示 ADAR1 与 ITGA2 之间存在正相关。最后，当我们应用原位异种移植小鼠模型时，证实了 ADAR1 p110 促进 HCC 转移。
ADAR1 通过增加 ITGA2 的表达促进肿瘤细胞黏附 ECM，从而增强 HCC 的转移。这一现象为更好地了解 HCC 转移过程的机制提供了新的信息。
