Generation of induced pluripotent stem cells (iPSCs) has been described as a powerful method to dedifferentiate the specialized cells to pluripotency. However, obtaining cancer-specific iPS cells (iPCs) encounters several barriers. The generation of iPCs provides valuable experimental platforms to mimic oncogenesis and offers potentials regarding drug screening. To overcome the difficulties regarding the iPC generation, we aimed at optimizing the generation of iPCs from glioblastoma multiform (GBM) cell lines and at understanding the potential barriers ahead of this process. The T731, T653, and mouse embryonic fibroblast cells were transduced by using retroviral plasmids encoding Oct4, Sox2, and Klf4. The cells were cultured on a layer of feeder cells for 14 days in iPS media and the obtained colonies were then picked and expanded to be evaluated for pluripotency markers by alkaline phosphatase staining, qRT-PCR, and Western blotting. Our findings confirmed resistance in cancer cells to achieve the pluripotency markers. In addition to designing technical tricks to obviate the barriers ahead of iPC generation, we suggested the small molecule PD98059 to enhance the efficiency of iPC generation from GBM cell lines. The resulting iPCs can further be used as a platform to study the mechanism of cancer formation and as a tool for drug screening for the treatment of patients with GBM.

中文翻译：

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从胶质母细胞瘤多种形式的细胞系中诱导多能性癌细胞的生成。

诱导多能干细胞（iPSC）的生成已被描述为一种将特化细胞去分化为多能性的有力方法。但是，获得癌症特异性iPS细胞（iPC）会遇到一些障碍。iPC的产生为模仿肿瘤发生提供了有价值的实验平台，并提供了有关药物筛选的潜力。为了克服有关iPC生成的困难，我们旨在优化多形性胶质母细胞瘤（GBM）细胞系生成iPC的过程，并希望了解此过程之前的潜在障碍。通过使用编码Oct4，Sox2和Klf4的逆转录病毒质粒转导T731，T653和小鼠胚胎成纤维细胞。将细胞在iPS培养基中的饲养细胞层上培养14天，然后挑选并扩增获得的菌落，并通过碱性磷酸酶染色，qRT-PCR和Western印迹法评估多能性标记。我们的发现证实了癌细胞中的耐药性以实现多能性标记。除了设计技术技巧以消除iPC产生之前的障碍外，我们还建议使用小分子PD98059增强来自GBM细胞系的iPC产生的效率。所得的iPC可以进一步用作研究癌症形成机理的平台，并用作治疗GBM患者的药物筛选工具。我们的发现证实了癌细胞中的耐药性以实现多能性标记。除了设计技术技巧以消除iPC产生之前的障碍外，我们还建议使用小分子PD98059增强来自GBM细胞系的iPC产生的效率。所得的iPC可以进一步用作研究癌症形成机理的平台，并用作治疗GBM患者的药物筛选工具。我们的发现证实了癌细胞中的耐药性以实现多能性标记。除了设计技术技巧以消除iPC产生之前的障碍外，我们还建议使用小分子PD98059增强来自GBM细胞系的iPC产生的效率。所得的iPC可以进一步用作研究癌症形成机理的平台，并用作治疗GBM患者的药物筛选工具。