Gamma-smooth muscle actin expression is associated with epithelial-mesenchymal transition and stem-like properties in hepatocellular carcinoma.

Gamma-smooth muscle actin expression is associated with epithelial-mesenchymal transition and stem-like properties in hepatocellular carcinoma.
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γ-平滑肌肌肉肌动蛋白的表达与肝细胞癌中的上皮间质转变和类似茎样性质有关。

DOI:
10.1371/journal.pone.0130559
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Guettier C
Guettier C
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Benzoubir N;Mussini C;Lejamtel C;Dos Santos A;Guillaume C;Desterke C;Samuel D;Bréchot C;Bourgeade MF;Guettier C

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肝细胞癌(HCC)的预后受到频繁的肿瘤复发和转移的阻碍。上皮-间充质转化(EMT)是肿瘤侵袭、转移和肿瘤起始细胞产生的关键过程。从新的间充质标记物的表达中对肿瘤样本中EMT的形态学鉴定可以提供相关的预后信息,并有助于理解转移过程。平滑肌肌动蛋白的表达进行了研究,在诱导EMT过程中培养的肝细胞和成人和儿童HCC系列的肝脏标本中使用免疫荧光和免疫组化测定。我们在此报告,在用TGF-β处理的HCC细胞系和HCC标本中,αSMA(一种已知的EMT间充质标志物)的表达从未被检测到。此外,我们的体外研究将SMA的肠溶形式γSMA确定为EMT的标志物。此外,这种SMA亚型在42名成人HCC患者的58个肿瘤中的46%和12名儿童HCC患者的16个肿瘤中的90%中表达。有趣的是,这种表达与肿瘤分化不良和以EpCAM和K19表达为特征的祖细胞特征显著相关。综上所述,我们的研究结果支持以下结论:HCC中γSMA的表达与EMT过程、HCC侵袭性和癌症干细胞的鉴定密切相关。这种相关性表明γSMA是预测HCC进展的一种新的强有力的标志物。
The prognosis of hepatocellular carcinoma (HCC) is hampered by frequent tumour recurrence and metastases. Epithelial-Mesenchymal Transition (EMT) is now recognized as a key process in tumour invasion, metastasis and the generation of cancer initiating cells. The morphological identification of EMT in tumour samples from the expression of novel mesenchymal markers could provide relevant prognostic information and aid in understanding the metastatic process. The expression of Smooth Muscle Actins was studied using immunofluorescence and immunohistochemistry assays in cultured liver cells during an induced EMT process and in liver specimens from adult and paediatric HCC series. We report here that in HCC cell lines treated with TGF-β and in HCC specimens, the expression of αSMA, a known mesenchymal marker of EMT, could never be detected. In addition, our in vitro studies identified the enteric form of SMA, γSMA, as being a marker of EMT. Moreover, this SMA isoform was expressed in 46% of 58 tumours from 42 adult HCC patients and in 90% of 16 tumours from 12 paediatric HCC patients. Interestingly, this expression was significantly correlated with poor tumour differentiation and progenitor cell features characterized by the expression of EpCAM and K19. Taken together, our results support the conclusion that γSMA expression in HCC is strongly correlated with the EMT process, HCC aggressiveness and the identification of cancer stem cells. This correlation suggests that γSMA represents a novel and powerful marker to predict HCC progression.
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