Liu Hongzhi, Wang Yingchao, Xing Xiaohua, Sun Ying, Wei Dahai, Chen Geng, Liu Qinying, Chen Shanshan, Liu Xiaolong, Liu Jingfeng
Liver Disease Center, The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian 350025, P.R. China.
Oncol Lett. 2018 Jul;16(1):335-345. doi: 10.3892/ol.2018.8666. Epub 2018 May 8.
Metastasis and recurrence following surgery are major reasons for the high mortality rate and poor prognosis associated with hepatocellular carcinoma (HCC). Cancer stem cells (CSCs) are thought to be able to cause cancer, and to be the primary cause of tumor recurrence and metastasis. The underlying mechanisms of the metastatic potential of CSCs is poorly understood. In the present study, side population (SP) cells were isolated from 4 HCC cell lines, and their self-renewal and migratory abilities were compared. The results demonstrate that SP cells from different cell lines exhibited similar self-renewal abilities but different metastatic potentials. Furthermore, the overall proteomes of the SP cells were systematically quantified. This revealed 11 and 19 differentially expressed proteins (DEPs), upregulated and downregulated, respectively, associated with increased metastatic potential. These proteins were involved in the 'regulation of mRNA processing' and 'cytoskeleton organization' biological processes. The majority of the proteins were involved in 'cell proliferation', 'migration' and 'invasion of cancer', and may promote HCC metastasis in a synergistic manner. The AKT and nuclear factor-κB signaling pathways may contribute to the regulation of HCC metastasis through regulating the DEPs in SP cells. To the best of our knowledge, the present study is the first to demonstrate the overall proteome difference among SP cells from the different HCC cell lines with different metastatic potentials. The present study provides novel information regarding the metastatic potential of CSCs, which will facilitate further investigation of the topic.
手术后继发转移和复发是肝细胞癌（HCC）死亡率高和预后差的主要原因。癌症干细胞（CSCs）被认为能够引发癌症，并且是肿瘤复发和转移的主要原因。目前对CSCs转移潜能的潜在机制了解甚少。在本研究中，从4种肝癌细胞系中分离出侧群（SP）细胞，并比较了它们的自我更新和迁移能力。结果表明，来自不同细胞系的SP细胞表现出相似的自我更新能力，但转移潜能不同。此外，还对SP细胞的整体蛋白质组进行了系统定量。这揭示了11种和19种差异表达蛋白（DEPs），分别上调和下调，与转移潜能增加相关。这些蛋白质参与了“mRNA加工调控”和“细胞骨架组织”生物学过程。大多数蛋白质参与“细胞增殖”、“迁移”和“癌症侵袭”，可能以协同方式促进肝癌转移。AKT和核因子-κB信号通路可能通过调节SP细胞中的DEPs来参与肝癌转移的调控。据我们所知，本研究首次证明了具有不同转移潜能的不同肝癌细胞系的SP细胞之间的整体蛋白质组差异。本研究提供了关于CSCs转移潜能的新信息，这将有助于对该主题的进一步研究。
