CD133+肝癌干细胞抵抗干扰素-γ诱导的自噬。
CD133+ liver cancer stem cells resist interferon-gamma-induced autophagy.
作者信息
Li Jian, Chen Jin-Na, Zeng Ting-Ting, He Fan, Chen Shu-Peng, Ma Stephanie, Bi Jiong, Zhu Xiao-Feng, Guan Xin-Yuan
机构信息
Department of Clinical Laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Room 102, 107 W. Yanjiang Road, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
出版信息
BMC Cancer. 2016 Jan 13;16:15. doi: 10.1186/s12885-016-2050-6.
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.
CONCLUSION
CD133(+) HCC CSCs resisted IFN-γ-induced autophagy, which might also be a mechanism through which CSCs resist immune eradication.
背景
肝细胞癌（HCC）是全球最致命的恶性肿瘤之一，而CD133是一种常用于肝细胞癌的癌症干细胞（CSC）标志物。据报道，CD133(+) CSCs对传统化疗和放疗具有抗性，但它们对免疫监视的反应却知之甚少。干扰素-γ（IFN-γ）是免疫系统产生的用于根除癌细胞的关键细胞因子之一，因此我们在本研究中调查了IFN-γ对CD133+肝癌CSCs的作用。
方法
通过功能测定（细胞增殖测定和裸鼠肿瘤形成）、流式细胞术、免疫荧光染色和RNA干扰来检测CD133(+)细胞对IFN-γ的反应。
结果
我们发现，IFN-γ在体内和体外（裸鼠）均可抑制CD133(+)细胞比例较低的细胞系（野生型人细胞、BEL7402、QGY7701）的增殖，但不影响CD133(+)细胞比例较高的细胞系（野生型人细胞、Huh7、PLC8024）的增殖。流式细胞术分析表明，用IFN-γ处理低CD133(+)细胞系后，CD133+细胞的比例增加。此外，IFN-γ诱导低CD133(+)细胞系的自噬以减少增殖。
结论
CD133(+)肝癌CSCs对IFN-γ诱导的自噬具有抗性，这也可能是CSCs抵抗免疫清除的一种机制。
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