Emma L Curry, Mohammad Moad, Craig N Robson, Rakesh Heer, Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, Newcastle University, Framlington Place, NE2 4HH Newcastle upon Tyne, United Kingdom.
World J Stem Cells. 2015 Mar 26;7(2):461-9. doi: 10.4252/wjsc.v7.i2.461.
Cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis are limited by lack of appropriate models for the development and pathogenesis of the disease based on human tissues. Primary culture of patient samples can help but is difficult to grow for a number of tissues. A potential opportunity to overcome these barriers is based on the landmark study by Yamanaka which demonstrated the ability of four factors; Oct4, Sox2, Klf4, and c-Myc to reprogram human somatic cells in to pluripotency. These cells were termed induced pluripotent stem cells (iPSCs) and display characteristic properties of embryonic stem cells. This technique has a wide range of potential uses including disease modelling, drug testing and transplantation studies. Interestingly iPSCs also share a number of characteristics with cancer cells including self-renewal and proliferation, expression of stem cell markers and altered metabolism. Recently, iPSCs have been generated from a number of human cancer cell lines and primary tumour samples from a range of cancers in an attempt to recapitulate the development of cancer and interrogate the underlying mechanisms involved. This review will outline the similarities between the reprogramming process and carcinogenesis, and how these similarities have been exploited to generate iPSC models for a number of cancers.
癌症是一组高度异质性的疾病，尽管治疗方法有所改善，但仍很普遍，每年有超过 1400 万例新发病例和 820 万人死亡。由于缺乏基于人体组织的疾病发展和发病机制的适当模型，对致癌过程的研究受到限制。患者样本的原代培养可能会有所帮助，但许多组织的培养都很困难。一个潜在的机会是基于 Yamanaka 的里程碑式研究，该研究表明，四种因子（Oct4、Sox2、Klf4 和 c-Myc）能够将人类体细胞重编程为多能性。这些细胞被称为诱导多能干细胞（iPSCs），并显示出胚胎干细胞的特征属性。该技术具有广泛的潜在用途，包括疾病建模、药物测试和移植研究。有趣的是，iPSCs 还与癌细胞具有许多共同特征，包括自我更新和增殖、干细胞标志物的表达和代谢改变。最近，已经从多种人类癌细胞系和多种癌症的原发性肿瘤样本中生成了 iPSCs，试图重现癌症的发展，并探究涉及的潜在机制。这篇综述将概述重编程过程和致癌作用之间的相似之处，以及如何利用这些相似之处生成多种癌症的 iPSC 模型。
