Cell Type-Specific TGF-β Mediated EMT in 3D and 2D Models and Its Reversal by TGF-β Receptor Kinase Inhibitor in Ovarian Cancer Cell Lines
Cell Type-Specific TGF-β Mediated EMT in 3D and 2D Models and Its Reversal by TGF-β Receptor Kinase Inhibitor in Ovarian Cancer Cell Lines
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DOI：
10.3390/ijms20143568
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发表时间：
2019-07-02
影响因子：
5.6
通讯作者：
Karedath, Thasni
中科院分区：
文献类型：
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作者：
Al Ameri, Wafa;Ahmed, Ikhlak;Karedath, Thasni
在不同的癌细胞系中，3D模型和2D模型的转录组图谱显示，转化生长因子-β介导的途径和细胞黏附途径的表达存在差异。在这些细胞系中，转化生长因子-β的存在显示出增加的侵袭潜力，这是特定于细胞类型的。在目前的研究中，我们发现外源性添加转化生长因子-β可以在一些癌细胞系中诱导上皮向间充质转化(EMT)。对不同卵巢癌细胞系进行RNA测序和实时荧光定量聚合酶链式反应(Real Time PCR)，以鉴定分子图谱和代谢图谱。由于转化生长因子-β诱导的EMT是细胞类型特异性的，我们决定选择两个有希望的卵巢癌细胞系作为研究EMT的模型系统。在SKOV3和CAOV3细胞株的2D和3D模型中，成功地描述了转化生长因子-β在EMT和肿瘤侵袭中的调控作用。3D和2D模型的功能评估表明，外源性转化生长因子-β的加入可以通过将癌细胞转化为侵袭性表型来诱导癌细胞的EMT和侵袭。转化生长因子-β受体激酶I抑制剂(LY364947)可逆转这些细胞的转化生长因子-β效应。总之，转化生长因子-β可以诱导EMT和迁移，增加侵袭力，增加细胞存活率，改变细胞特性，重塑细胞外基质，增加细胞代谢，有利于肿瘤的侵袭和转移。我们的结论是，转化生长因子-β及其抑制物的转录和表型效应是细胞类型特异性的，而不是癌症特异性的。
Transcriptome profiling of 3D models compared to 2D models in various cancer cell lines shows differential expression of TGF-beta-mediated and cell adhesion pathways. Presence of TGF-beta in these cell lines shows an increased invasion potential which is specific to cell type. In the present study, we identified exogenous addition of TGF-beta can induce Epithelial to Mesenchymal Transition (EMT) in a few cancer cell lines. RNA sequencing and real time PCR were carried out in different ovarian cancer cell lines to identify molecular profiling and metabolic profiling. Since EMT induction by TGF- beta is cell-type specific, we decided to select two promising ovarian cancer cell lines as model systems to study EMT. TGF-beta modulation in EMT and cancer invasion were successfully depicted in both 2D and 3D models of SKOV3 and CAOV3 cell lines. Functional evaluation in 3D and 2D models demonstrates that the addition of the exogenous TGF- beta can induce EMT and invasion in cancer cells by turning them into aggressive phenotypes. TGF-beta receptor kinase I inhibitor (LY364947) can revert the TGF-beta effect in these cells. In a nutshell, TGF-beta can induce EMT and migration, increase aggressiveness, increase cell survival, alter cell characteristics, remodel the Extracellular Matrix (ECM) and increase cell metabolism favorable for tumor invasion and metastasis. We concluded that transcriptomic and phenotypic effect of TGF-beta and its inhibitor is cell-type specific and not cancer specific.