摘要
异质型细胞叠套结构(heterotypic cell-in-cell structure,heCICs)与肿瘤发生和发展密切相关,在生命科学研究中的重要性逐渐显露。Ras相关C3肉毒毒素底物1(Ras-related C3 botulinum toxin substrate 1,Rac1)属于经典的Rho GTP酶,在细胞骨架以及细胞运动中起到关键调控作用。为研究Rac1在he CICs形成中的作用和机制,利用活细胞示踪剂cell-tracker分别标记肿瘤细胞和免疫杀伤细胞,建立heCICs模型。利用Rac1抑制剂NSC23766抑制Rac1活性后发现,肿瘤细胞与免疫杀伤细胞之间的heCICs形成率显著降低。通过分子克隆技术获得重组质粒pQCXIP-Rac1-EGFP,进行病毒包装感染肿瘤细胞获得Rac1过表达细胞系。进一步检测Rac1过表达对heCICs形成能力的影响,结果表明,Rac1表达水平升高后,heCICs形成率显著升高。本研究显示Rac1具有促进he CICs形成的作用,这为Rac1作为细胞叠套相关疾病的药物治疗靶点奠定了研究基础。
Heterotypic cell-in-cell structures(heCICs)are closely related to tumor development and progression,and have become a new frontier in life science research.Ras-related C3 botulinum toxin substrate 1(Rac1)belongs to the classic Rho GTPase,which plays a key role in regulating the cytoskeleton and cell movement.To investigate the role and mechanism of Rac1 in the formation of heCICs,tumor cells and immune killer cells were labeled with cell-tracker,respectively,to establish the heCICs model.Upon treatment with the Rac1 inhibitor NSC23766,the formation of heCICs between tumor and immune cells was significantly reduced.The plasmid pQCXIP-Rac1-EGFP constructed by gene cloning was packaged into pseudoviruses that subsequently infect tumor cells to make cell lines stably expressing Rac1.As a result,the formation of heCICs was significantly increased upon Rac1 overexpression.These results demonstrated a promotive role of Rac1 in heCICs formation,which may facilitate treating cell-in-cell related diseases,such as tumors,by targeting Rac1.
作者
胡涛
冯鹏飞
李浩源
周鲁林
牛祖彪
黄一诺
王小宁
王晨曦
刘惠
吴成君
HU Tao;FENG Pengfei;LI Haoyuan;ZHOU Lulin;NIU Zubiao;HUANG Yinuo;WANG Xiaoning;WANG Chenxi;LIU Hui;WU Chengjun(School of Biomedical Engineering,Dalian University of Technology,Dalian 116024,Liaoning,China;Beijing Institute of Biotechnology,Academy of Military Medical Sciences,Beijing 100071,China;Chinese People’s Liberation Army Medical School,Beijing 100853,China;Beijing Key Laboratory of Aging and Geriatrics,Institute of Geriatrics,the 2nd Medical Center,China National Clinical Research Center for Geriatric Disease,Chinese People’s Liberation Army General Hospital,Beijing 100853,China;Department of Geriatric Hematology and Oncology,Shandong Provincial Hospital Affiliated to Shandong First Medical University,Jinan 250021,Shandong,China;Beijing Key Laboratory of Therapeutics Vaccines,Department of Oncology,Beijing Shijitan Hospital of Capital Medical University,Beijing 100038,China)
出处
《生物工程学报》
CAS
CSCD
北大核心
2023年第10期4123-4134,共12页
Chinese Journal of Biotechnology
基金
国家自然科学基金(82072287,32100608)。
