title: CD133+ liver cancer stem cells resist interferon-gamma-induced autophagy.
abstract: BACKGROUND
  Hepatocellular carcinoma (HCC) is one of the most fatal malignancies worldwide, and CD133 is a popular cancer stem cell (CSC) marker for HCC. CD133(+) CSCs have been reported to resist conventional chemo- and radiotherapy, but little is known about their response to immune surveillance. Interferon-gamma (IFN-γ) is one of key cytokines that the immune system produce to eradicate cancer cells, so we investigated the function of IFN-γ on CD133+ HCC CSCs in this study.
  
  
  METHODS
  The response of CD133(+) cells to IFN-γ was performed with functional assays (cell proliferation assay and tumor formation in nude mice), flow cytometry, immunofluorescence staining and RNA interference.
  
  
  RESULTS
  We found that IFN-γ inhibited the proliferation of cell lines with low percentage of CD133(+) cells (wild-type human cells, BEL7402, QGY7701) but it did not affect the proliferation of cell lines with high percentage of CD133(+) cells (wild-type human cells, Huh7, PLC8024) in vivo and in vitro (nude mice). Flow cytometry analysis demonstrated that the percentage of CD133+ cells increased after IFN-γ treatment of low CD133(+) cell lines. Furthermore, IFN-γ induced the autophagy of low CD133(+) cell lines to decrease proliferation.
  
  
  CONCLUSIONS
  CD133(+) HCC CSCs resisted IFN-γ-induced autophagy, which might also be a mechanism through which CSCs resist immune eradication.
authors.affiliation: Department of Clinical Laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Room 102, 107 W. Yanjiang Road, Guangzhou, 510120, China. lijian57@mail.sysu.edu.cn.|Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. lijian57@mail.sysu.edu.cn.|State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China. lijian57@mail.sysu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. jinnachan2010@gmail.com.
authors.forename: Jin-Na
authors.initials: JN
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China. zengtt@sysucc.org.cn.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zeng
authors.affiliation: Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. hefan2@mail2.sysu.edu.cn.
authors.forename: Fan
authors.initials: F
authors.lastname: He
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China. chenshp@sysucc.org.cn.
authors.forename: Shu-Peng
authors.initials: SP
authors.lastname: Chen
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. stephanie.ma@gmail.com.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. bijiong2000@hotmail.com.
authors.forename: Jiong
authors.initials: J
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China. zhuxfeng@mail.sysu.edu.cn.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, PR China. xyguan@hkucc.hku.hk.|Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. xyguan@hkucc.hku.hk.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics*; D001343:Autophagy / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse; D007371:Interferon-gamma