Exploring stemness gene expression and vasculogenic mimicry capacity in well- and poorly-differentiated hepatocellular carcinoma cell lines
Exploring stemness gene expression and vasculogenic mimicry capacity in well- and poorly-differentiated hepatocellular carcinoma cell lines
复制标题
DOI：
10.1016/j.bbrc.2012.05.009
复制
发表时间：
2012-06-08
影响因子：
3.1
通讯作者：
Svasti, Jisnuson
中科院分区：
文献类型：
--
作者：
Lirdprapamongkol, Kriengsak;Chiablaem, Khajeelak;Svasti, Jisnuson
血管生成拟态（VM）是癌细胞通过形成血管模仿内皮细胞的现象。已经提出干细胞样表型参与这种肿瘤可塑性。VM似乎与转移率相关，但目前尚无关于促转移和促血管生成因子或肝细胞生长因子（HGF）和血管内皮生长因子（VEGF）对肝细胞癌（HCC）细胞VM形成的影响的报道。在这里，我们确定了高分化和低分化肝癌细胞系中的VM容量和干性基因（Oct 4、Sox 2、Nanog和CD 133）的表达。具有间充质特征的低分化细胞系SK-Hep-1（高侵袭性和表达Vimentin，不含E-cadherin）在体外可形成VM，而高分化细胞系HepG 2不形成VM。干性基因的表达与内源VM能力之间没有相关性。然而，HGF而不是VEGF，可以诱导HepG 2中VM的形成，伴随着上皮间质转化（EMT），去分化和干细胞基因的表达增加。我们的研究结果表明，干细胞基因在肝癌细胞VM能力中的作用可能取决于分化状态。(c)2012 Elsevier Inc. All rights reserved.
Vasculogenic mimicry (VM) is the phenomenon where cancer cells mimic endothelial cells by forming blood vessels. A stem cell-like phenotype has been proposed to be involved in this tumor plasticity. VM seems to correlate with metastasis rate, but there have been no reports on the effects of pro-metastatic and pro-angiogenic factors or hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) on VM formation of hepatocellular carcinoma (HCC) cells. Here, we determine VM capacity and expression of stemness genes (Oct4, Sox2, Nanog and CD133) in well- and poorly-differentiated HCC cell lines. The poorly-differentiated cell line SK-Hep-1 with mesenchymal features (high invasiveness and expressing Vimentin, with no E-cadherin) could form VM in vitro, while the well-differentiated cell line HepG2 did not form VM. There was no correlation between expression of stemness genes and intrinsic VM capacity. However, HGF but not VEGF, could induce VM formation in HepG2, concomitant with epithelial-mesenchymal transition (EMT), de-differentiation and increased expression of stemness genes. Our results show that the role of stemness genes in VM capacity of HCC cells is likely to depend on differentiation status. (c) 2012 Elsevier Inc. All rights reserved.