Malfettone Andrea, Soukupova Jitka, Bertran Esther, Crosas-Molist Eva, Lastra Raquel, Fernando Joan, Koudelkova Petra, Rani Bhavna, Fabra Ángels, Serrano Teresa, Ramos Emilio, Mikulits Wolfgang, Giannelli Gianluigi, Fabregat Isabel
Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet, Barcelona, Spain.
Department of Surgery, Liver Transplant Unit, University Hospital of Bellvitge, Barcelona, Spain.
Cancer Lett. 2017 Apr 28;392:39-50. doi: 10.1016/j.canlet.2017.01.037. Epub 2017 Feb 2.
As part of its potential pro-tumorigenic actions, Transforming Growth Factor-(TGF)-β induces epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells. Whether EMT induces changes in tumor cell plasticity has not been fully explored yet. Here, we analyze the effects of TGF-β on the EMT and stem-related properties of HCC cells and the potential correlation among those processes. The translational aim of the study was to propose a TGF-β/EMT/stem gene signature that would help in recognizing HCC patients as good candidates for anti-TGF-β therapy. Results indicate that when TGF-β induces EMT in HCC cells, a switch in the expression of stem genes is observed and their stemness potential and migratory/invasive capacity are enhanced. However, TGF-β may induce a partial EMT in some epithelial HCC cells, increasing the expression of mesenchymal genes and CD44, but maintaining epithelial gene expression. Epithelial cells show higher stemness potential than the mesenchymal ones, but respond to TGF-β increasing their migratory and invasive capacity. In HCC patient samples, TGFB1 expression most frequently correlates with a partial EMT, increase in mesenchymal genes and CD44 expression, as well as maintenance or over-expression of epithelial-related genes.
作为其潜在的促肿瘤发生作用的一部分，转化生长因子-β（TGF-β）可诱导肝细胞癌（HCC）细胞发生上皮-间质转化（EMT）。EMT是否会诱导肿瘤细胞可塑性的变化尚未得到充分研究。在此，我们分析了TGF-β对HCC细胞的EMT和干细胞相关特性的影响以及这些过程之间的潜在相关性。该研究的转化目标是提出一种TGF-β/EMT/干细胞基因特征，这将有助于识别适合抗TGF-β治疗的HCC患者。结果表明，当TGF-β诱导HCC细胞发生EMT时，可观察到干细胞基因表达的转变，其干性潜能以及迁移/侵袭能力增强。然而，TGF-β可能在一些上皮性HCC细胞中诱导部分EMT，增加间充质基因和CD44的表达，但维持上皮基因表达。上皮细胞比间充质细胞表现出更高的干性潜能，但对TGF-β有反应，增加其迁移和侵袭能力。在HCC患者样本中，TGFB1表达最常与部分EMT、间充质基因和CD44表达增加以及上皮相关基因的维持或过表达相关。
