Chen Jianfeng, Ding Peipei, Li Ling, Gu Hongyu, Zhang Xin, Zhang Long, Wang Na, Gan Lu, Wang Qi, Zhang Wei, Hu Weiguo
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China; Department of Immunology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai 200032, China.
Stem Cell Reports. 2017 Jan 10;8(1):140-151. doi: 10.1016/j.stemcr.2016.11.008. Epub 2016 Dec 22.
Cancer stem cells (CSCs) are highly associated with therapy resistance and metastasis. Interplay between CSCs and various immune components is required for tumor survival. However, the response of CSCs to complement surveillance remains unknown. Herein, using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, we found that CD59 was upregulated to protect CSCs from complement-dependent cytotoxicity. CD59 silencing significantly enhanced complement destruction and completely suppressed tumorigenesis in CSC-xenografted nude mice. Furthermore, we identified that SOX2 upregulates CD59 in epithelial CSCs. In addition, we revealed that SOX2 regulates the transcription of mCd59b, leading to selective mCD59b abundance in murine testis spermatogonial stem cells. Therefore, we demonstrated that CD59 regulation by SOX2 is required for stem cell evasion of complement surveillance. This finding highlights the importance of complement surveillance in eliminating CSCs and may suggest CD59 as a potential target for cancer therapy.
癌症干细胞（CSCs）与治疗抗性和转移高度相关。肿瘤存活需要CSCs与各种免疫成分之间的相互作用。然而，CSCs对补体监测的反应仍然未知。在此，我们使用从乳腺肿瘤和肺腺癌细胞系制备的类干细胞球形成细胞，发现CD59上调以保护CSCs免受补体依赖性细胞毒性作用。CD59沉默显著增强补体破坏，并完全抑制CSC异种移植裸鼠中的肿瘤发生。此外，我们确定SOX2在上皮CSCs中上调CD59。此外，我们揭示SOX2调节mCd59b的转录，导致小鼠睾丸精原干细胞中选择性mCD59b丰度。因此，我们证明SOX2对CD59的调节是干细胞逃避补体监测所必需的。这一发现突出了补体监测在消除CSCs中的重要性，并可能提示CD59作为癌症治疗的潜在靶点。
