CD133+ liver cancer stem cells resist interferon-gamma-induced autophagy. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Li, Jian; Chen, Jin-Na; Zeng, Ting-Ting; He, Fan; Chen, Shu-Peng; Ma, Stephanie; Bi, Jiong; Zhu, Xiao-Feng; Guan, Xin-Yuan
• Is Part Of: BMC cancer. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 11
• Publication Date: 2016-12
• Subjects: HCC -- CSC -- CD133 -- Immune -- IFN-γ -- Autophagy; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-016-2050-6
• Languages: English
• ISSNs: 1471-2407

Abstract

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. Conclusion CD133+ HCC CSCs resisted IFN-γ-induced autophagy, which might also be a mechanism through which CSCs resist immune eradication.