CD133+ liver cancer stem cells resist interferon-gamma-induced autophagy

BMC Cancer

Research Article

Jian Li¹  Jin-Na Chen²  Stephanie Ma²  Fan He³  Jiong Bi⁴  Ting-Ting Zeng⁵  Shu-Peng Chen⁵  Xiao-Feng Zhu⁵  Xin-Yuan Guan⁶ 

[1] Department of Clinical Laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Room 102, 107 W. Yanjiang Road, 510120, Guangzhou, China;Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China;State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, 510060, Guangzhou, Guangdong, PR China;Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;Department of Forensic Medicine, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China;Department of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, 510060, Guangzhou, Guangdong, PR China;State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, 510060, Guangzhou, Guangdong, PR China;Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;

关键词: HCC;    CSC;    CD133;    Immune;    IFN-γ;    Autophagy;   

DOI  :  10.1186/s12885-016-2050-6

 received in 2015-07-02, accepted in 2016-01-06,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHepatocellular 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.MethodsThe 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.ResultsWe 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.ConclusionCD133+ HCC CSCs resisted IFN-γ-induced autophagy, which might also be a mechanism through which CSCs resist immune eradication.

【 授权许可】

CC BY   
© Li et al. 2016