A novel model of liver cancer stem cells developed from induced pluripotent stem cells
A novel model of liver cancer stem cells developed from induced pluripotent stem cells
复制标题
DOI：
10.1038/s41416-020-0792-z
复制
发表时间：
2020-03-17
影响因子：
8.8
通讯作者：
Seno, Masaharu
中科院分区：
文献类型：
--
作者：
Afify, Said M.;Calle, Anna Sanchez;Seno, Masaharu
肝癌是癌症相关死亡的第二大常见原因。包括肝癌在内的所有肿瘤都含有癌症干细胞（CSCs）。迄今为止，调节肝CSCs发育的分子机制尚不清楚。方法在肝细胞癌（HCC）细胞系Huh7细胞条件培养基（CM）中转化小鼠诱导多能干细胞（miPSCs），建立一种新的肝CSCs模型。将CM处理的miPSCs注射到BALB/c裸鼠肝脏中。然后切除发展的肿瘤并进行分析。结果原代培养的恶性肿瘤细胞具有自我更新能力、分化潜力和体内致瘤性，具有丰富的肝癌相关标志物和CSC标志物。结论建立了肝干细胞从miPS转化的模型，并在转化过程中表现出不同阶段的干细胞性。我们的CSC模型对于评估发展肝脏CSC所需的分子机制非常重要，并且可以帮助战胜肝癌。
Background Liver cancer is the second most common cause of cancer-related death. Every type of tumours including liver cancer contains cancer stem cells (CSCs). To date, the molecular mechanism regulating the development of liver CSCs remains unknown. Methods In this study, we tried to generate a new model of liver CSCs by converting mouse induced pluripotent stem cells (miPSCs) with hepatocellular carcinoma (HCC) cell line Huh7 cells conditioned medium (CM). miPSCs treated with CM were injected into the liver of BALB/c nude mice. The developed tumours were then excised and analysed. Results The primary cultured cells from the malignant tumour possessed self-renewal capacity, differentiation potential and tumorigenicity in vivo, which were found rich in liver cancer-associated markers as well as CSC markers. Conclusions We established a model of liver CSCs converting from miPS and showed different stages of stemness during conversion process. Our CSC model will be important to assess the molecular mechanisms necessary to develop liver CSCs and could help in defeating liver cancer.