Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors
文献类型：期刊论文
| 作者 | Jiang, Zhiwu8; Cheng, Lin9; Wu, Zhiping8; Zhou, Linfu8; Wang, Haitao1; Hong, Qilan9; Wu, Qiting8; Long, Youguo8; Huang, Yunlin8; Xu, Gaoqi9 |
| 刊名 | EMBO REPORTS
 |
| 出版日期 | 2022-04-19 |
| 页码 | 17 |
| ISSN号 | 1469-221X |
| 关键词 | biomarkers hepatocellular carcinoma humanized mouse models immunotherapy oncogenes |
| DOI | 10.15252/embr.202154275 |
| 通讯作者 | Li, Yinxiong(li_yinxiong@gibh.ac.cn) ; Li, Peng(li_peng@gibh.ac.cn) |
| 英文摘要 | Our understanding of human hepatocellular carcinoma (HCC) development and progression has been hampered by the lack of in vivo models. We performed a genetic screen of 10 oncogenes and genetic mutations in Fah-ablated immunodeficient mice in which primary human hepatocytes (PHHs) are used to reconstitute a functional human liver. We identified that MYC, TP53(R249S), and KRAS(G12D) are highly expressed in induced HCC (iHCC) samples. The overexpression of MYC and TP53(R249S) transform PHHs into iHCC in situ, though the addition of KRAS(G12D) significantly increases the tumorigenic efficiency. iHCC, which recapitulate the histological architecture and gene expression characteristics of clinical HCC samples, reconstituted HCC after serial transplantations. Transcriptomic analysis of iHCC and PHHs showed that MUC1 and FAP are expressed in iHCC but not in normal livers. Chimeric antigen receptor (CAR) T cells against these two surface markers efficiently lyse iHCC cells. The properties of iHCC model provide a biological basis for several clinical hallmarks of HCC, and iHCC may serve as a model to study HCC initiation and to identify diagnostic biomarkers and targets for cellular immunotherapy. |
| WOS关键词 | P53 GENE ; C-MYC ; LIVER ; MICE ; HETEROZYGOSITY ; PROGRESSION ; EXPRESSION ; MUTATIONS ; ETIOLOGY ; LEUKEMIA |
| 资助项目 | National Key Research and Development Plan[2021YFE0202800] ; National Key Research and Development Plan[2017YFE0131600] ; National Key Research and Development Plan[2019YFA0111500] ; National Natural Science Foundation of China[81961128003] ; National Natural Science Foundation of China[81972672] ; National Natural Science Foundation of China[81773301] ; National Natural Science Foundation of China[81870121] ; National Natural Science Foundation of China[81873847] ; National Natural Science Foundation of China[81872069] ; National Natural Science Foundation of China[32170946] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2020351] ; Guangdong Provincial Significant New Drugs Development[2019B020202003] ; Guangdong Provincial Significant New Drugs Development[2019A1515010062] ; Guangdong Provincial Significant New Drugs Development[2020A1515011516] ; Guangzhou Science and Technology Plan Project[201907010042] ; Guangzhou Science and Technology Plan Project[2020B1212060052] ; Frontier Research Program of the Guangzhou Regenerative Medicine and Health Guangdong Laboratory[2018GZR110105003] ; Science and Technology Planning Project of Guangdong Province, China[2020B1212060052] ; Science and Technology Program of Guangzhou, China[202002020083] ; Open project of the State Key Laboratory of Respiratory Disease[SKLRD-OP-202002] ; University Grants Committee/Research Grants Council of the Hong Kong[AoE/M-401/20] ; Innovation and Technology Fund (ITF) from Hong Kong SAR Government |
| WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000783458200001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/299737]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Yinxiong; Li, Peng |
| 作者单位 | 1.Univ Macau, Fac Hlth Sci, Canc Ctr, Macau, Peoples R China 2.Hunan Zhaotai Biomed Co Ltd, Changsha, Peoples R China 3.Guangzhou Med Univ, Affiliated Hosp 2, Guangzhou, Peoples R China 4.Sun Yat Sen Univ, Sch Publ Hlth, Dept Nutr, Guangdong Prov Key Lab Food, Guangzhou, Peoples R China 5.First Peoples Hosp Foshan, Clin Res Inst, Foshan, Guangdong, Peoples R China 6.Guangdong Women & Children Hosp, Guangzhou, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, Zhang Jiang Hitech Pk, Shanghai, Peoples R China 8.Chinese Acad Sci, Ctr Cell Regenerat & Biol Therapies, Guangzhou Inst Biomed & Hlth,Guangdong Prov Key L, China New Zealand Joint Lab Biomed & Hlth,State K, Guangzhou, Peoples R China 9.Guangzhou Regenerat Med & Hlth Guangdong Lab, Bioland Lab, Guangzhou, Peoples R China 10.Univ Hong Kong, Li Ka Shing Fac Med, Sch Biomed Sci Stem Cell & Regenerat Med Consorti, Hong Kong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Zhiwu,Cheng, Lin,Wu, Zhiping,et al. Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors[J]. EMBO REPORTS,2022:17. |
| APA | Jiang, Zhiwu.,Cheng, Lin.,Wu, Zhiping.,Zhou, Linfu.,Wang, Haitao.,...&Li, Peng.(2022).Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors.EMBO REPORTS,17. |
| MLA | Jiang, Zhiwu,et al."Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors".EMBO REPORTS (2022):17. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。