Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways  

作　　者：Xin-Xin Han Shengkai Jin Li-Ming Yu Min Wang Xin-Yu Hu Dai-Yu Hu Jie Ren Meng-Han Zhang Wei Huang Jia-Jia Deng Qing-Qing Chen Zhengliang Gao Hua He Chunhui Cai 

机构地区：[1]Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases,Shanghai Stomatological Hospital&School of Stomatology,Fudan University,Shanghai,China [2]Institute of Photomedicine,Shanghai Skin Disease Hospital,Tongji University School of Medicine,Shanghai,China [3]School of Medicine,Jiaxing University,Jiaxing,China [4]Tongji University Cancer Center,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,China [5]Department of Neurosurgery,Changzheng Hospital,Second Military Medical University,Shanghai,China [6]Department of Neurosurgery,Third Affiliated Hospital of Second Military Medical University,Shanghai,China

出　　处：《Cell Regeneration》2022年第1期212-226,共15页细胞再生（英文）

基　　金：This work was supported by funds from the National Natural Science Foundation of China[31600819 to CCH,81901031 to HXX,32070862 and 31571058 to GZL];the Shanghai Municipal Population and Family Planning Commission[20174Y0216 to CCH];the Natural Science Foundation of Shanghai[19ZR1445400 to HXX];the National Key R&D Program of China[2019YFA0110300];the Shanghai Easter Scholar[8101219003 to GZL].

摘　　要：Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential.The main reason is that malignant glioma holds key cluster cells,glioma stem cells(GSCs).GSCs contribute to tumorigenesis,tumor progression,recurrence,and treatment resistance.Interferon-beta(IFN-β)is well known for its anti-proliferative efficacy in diverse cancers.IFN-βalso displayed potent antitumor effects in malignant glioma.IFN-βaffect both GSCs and Neural stem cells(NSCs)in the treatment of gliomas.However,the functional comparison,similar or different effects of IFN-βon GSCs and NSCs are rarely reported.Here,we studied the similarities and differences of the responses to IFN-βbetween human GSCs and normal NSCs.We found that IFN-βpreferentially inhibited GSCs over NSCs.The cell body and nucleus size of GSCs increased after IFN-βtreatment,and the genomic analysis revealed the enrichment of the upregulated immune response,cell adhesion genes and down regulated cell cycle,ribosome pathways.Several typical cyclin genes,including cyclin A2(CCNA2),cyclin B1(CCNB1),cyclin B2(CCNB2),and cyclin D1(CCND1),were significantly downregulated in GSCs after IFN-βstimulation.We also found that continuous IFN-βstimulation after passage further enhanced the inhibitory effect.Our study revealed how genetic diversity resulted in differential effects in response to IFN-βtreatment.These results may contribute to improve the applications of IFN-βin anti-cancer immunotherapy.In addition,these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.

关 键 词：Glioma stem cells IFN-Β Neural stem cell Cell cycle Immune response 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]