Xue Gang, Ren Zhenxin, Grabham Peter W, Chen Yaxiong, Zhu Jiayun, Du Yarong, Pan Dong, Li Xiaoman, Hu Burong
Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China University of Chinese Academy of Sciences, Beijing, 100049, China.
Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Building 5-204, Lanzhou 730000, China.
J Radiat Res. 2015 Jul;56(4):656-62. doi: 10.1093/jrr/rrv018. Epub 2015 Apr 16.
In vitro 3D growth of tumors is a new cell culture model that more closely mimics the features of the in vivo environment and is being used increasingly in the field of biological and medical research. It has been demonstrated that cancer cells cultured in 3D matrices are more radio-resistant compared with cells in monolayers. However, the mechanisms causing this difference remain unclear. Here we show that cancer cells cultured in a 3D microenvironment demonstrated an increase in cells with stem cell properties. This was confirmed by the finding that cells in 3D cultures upregulated the gene and protein expression of the stem cell reprogramming factors such as OCT4, SOX2, NANOG, LIN28 and miR-302a, compared with cells in monolayers. Moreover, the expression of β-catenin, a regulating molecule of reprogramming factors, also increased in 3D-grown cancer cells. These findings suggest that cancer cells were reprogrammed to become stem cell-like cancer cells in a 3D growth culture microenvironment. Since cancer stem cell-like cells demonstrate an increased radio-resistance and chemo-resistance, our results offer a new perspective as to why. Our findings shed new light on understanding the features of the 3D growth cell model and its application in basic research into clinical radiotherapy and medicine.
肿瘤的体外三维生长是一种新的细胞培养模型，它更紧密地模拟体内环境的特征，并且在生物和医学研究领域中越来越多地被使用。已经证明，与单层培养的细胞相比，在三维基质中培养的癌细胞具有更高的放射抗性。然而，造成这种差异的机制仍不清楚。在这里，我们表明在三维微环境中培养的癌细胞表现出具有干细胞特性的细胞增加。这一点通过以下发现得到证实：与单层培养的细胞相比，三维培养的细胞上调了干细胞重编程因子如OCT4、SOX2、NANOG、LIN28和miR-302a的基因和蛋白质表达。此外，重编程因子的调节分子β-连环蛋白的表达在三维生长的癌细胞中也增加。这些发现表明，在三维生长培养微环境中癌细胞被重编程成为干细胞样癌细胞。由于干细胞样癌细胞表现出更高的放射抗性和化学抗性，我们的结果为其原因提供了一个新的视角。我们的发现为理解三维生长细胞模型的特征及其在临床放射治疗和医学基础研究中的应用提供了新的线索。
