Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers
Cancer Stem Cells are Depolarized Relative to Normal Stem Cells Derived from Human Livers
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DOI：
10.5604/16652681.1231590
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发表时间：
2017-04-01
影响因子：
3.8
通讯作者：
Minuk, Gerald Y.
中科院分区：
文献类型：
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作者：
Bautista, Wendy;Lipschitz, Jeremy;Minuk, Gerald Y.
前言和目的：无法区分癌症(CSCs)和正常干细胞(NSCs)，阻碍了寻找更安全、更有效的肝细胞癌治疗方法的尝试。本研究的目的是记录和比较分别来自人肝细胞癌和健康肝脏的CSCs和NSCs的细胞膜电位差异，并确定改变的GABA能神经支配是否可以解释这种差异。材料和方法：采用磁珠分离法从人肝组织中分离出上皮细胞黏附分子(EpCAM)阳性干细胞。新鲜分离细胞微电极穿刺法记录细胞PD。结果：CSCs去极化(-7.0+/-1.3 mV)较NSCs(-23.0+/-1.4 mV，p<；0.01)显著去极化。去极化状态与不同的GABAA受体亚单位表达谱有关，在CSCs中，以GAGAA？3亚基表达为代表的时相传递为主，而在NSC中，以GABAA？6亚基表达为代表的紧张性传递为主。此外，GABAA亚基？3、？3、？3和？在CSCs中强表达，而在GABAA？在NSCs中以表达为主。CSCs和NSCs对GABAA受体激动剂的反应相似(pD分别为12.5+/-1.2 mV和11.0+/-3.5 mV)。结论：CSCs相对于NSCs有明显的去极化作用，这种差异与GABAA受体亚单位表达的差异有关。它们共同为人类肝癌的发病机制和可能的治疗提供了新的见解。
INTRODUCTION AND AIM:The inability to distinguish cancer (CSCs) from normal stem cells (NSCs) has hindered attempts to identify safer, more effective therapies for hepatocellular carcinoma (HCC). The aim of this study was to document and compare cell membrane potential differences (PDs) of CSCs and NSCs derived from human HCC and healthy livers respectively and determine whether altered GABAergic innervation could explain the differences. MATERIAL AND METHODS:Epithelial cell adhesion molecule (EpCAM) positive stem cells were isolated from human liver tissues by magnetic bead separations. Cellular PDs were recorded by microelectrode impalement of freshly isolated cells. GABAA receptor subunit expression was documented by reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence.RESULTS:CSCs were significantly depolarized (-7.0 +/- 1.3 mV) relative to NSCs (-23.0 +/- 1.4 mV, p & lt; 0.01). The depolarized state was associated with different GABAA receptor subunit expression profiles wherein phasic transmission, represented by GAGAA ?3 subunit expression, was prevalent in CSCs while tonic transmission, represented by GABAA ?6 subunit expression, prevailed in NSCs. In addition, GABAA subunits ?3, ?3, ?3 and ? were strongly expressed in CSCs while GABAA ? expression was dominant in NSCs. CSCs and NSCs responded similarly to GABAA receptor agonists (?PD: 12.5 +/- 1.2 mV and 11.0 +/- 3.5 mV respectively).CONCLUSION:The results of this study indicate that CSCs are significantly depolarized relative to NSCs and these differences are associated with differences in GABAA receptor subunit expression. Together they provide new insights into the pathogenesis and possible treatment of human HCC.