Your browser doesn't support javascript.
loading
Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors.
Jiang, Zhiwu; Cheng, Lin; Wu, Zhiping; Zhou, Linfu; Wang, Haitao; Hong, Qilan; Wu, Qiting; Long, Youguo; Huang, Yunlin; Xu, Gaoqi; Yao, Yao; Tang, Zhaoyang; Zhang, Zhenfeng; Yang, Lili; Luo, Wei; Yang, Jie; Gong, Likun; Liu, Pentao; Chen, Xinwen; Cui, Shuzhong; Zhang, Qi; Li, Yinxiong; Li, Peng.
Afiliação
  • Jiang Z; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Cheng L; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.
  • Wu Z; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Zhou L; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Wang H; Cancer Center, Faculty of Health Sciences, University of Macau, Macau, China.
  • Hong Q; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.
  • Wu Q; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Long Y; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Huang Y; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Xu G; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.
  • Yao Y; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Tang Z; Hunan Zhaotai Biomedicine Co. Ltd., Changsha, China.
  • Zhang Z; The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • Yang L; Department of Nutrition, Guangdong Provincial Key Laboratory of Food, School of Public Health, Sun Yat-sen University, Guangzhou, China.
  • Luo W; Clinical Research Institute, The First People's Hospital of Foshan, Foshan, Guangdong, China.
  • Yang J; Guangdong Women and Children Hospital, Panyu, Guangzhou, China.
  • Gong L; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhang Jiang Hi-Tech Park, Shanghai, China.
  • Liu P; School of Biomedical Sciences, Stem Cell, and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Chen X; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Cui S; Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
  • Zhang Q; Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • Li Y; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
  • Li P; China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institutes of Biomedicine and Health, Chinese Academ
EMBO Rep ; 23(6): e54275, 2022 06 07.
Article em En | MEDLINE | ID: mdl-35437924
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, TP53R249S , and KRASG12D are highly expressed in induced HCC (iHCC) samples. The overexpression of MYC and TP53R249S transform PHHs into iHCC in situ, though the addition of KRASG12D 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.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article