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Rac1促进异质型细胞叠套结构的形成
引用本文: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.Rac1促进异质型细胞叠套结构的形成[J].生物工程学报,2023,39(10):4123-4134.
作者姓名: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
作者单位:大连理工大学生物医学工程学院, 辽宁 大连 116024;军事医学研究院生物工程研究所, 北京 100071;军事医学研究院生物工程研究所, 北京 100071;解放军医学院, 北京 100853;解放军总医院第二医学中心老年医学研究所 国家老年疾病临床医学研究中心 衰老与相关疾病研究北京市重点实验室, 北京 100853;军事医学研究院生物工程研究所, 北京 100071;山东第一医科大学附属省立医院老年血液肿瘤科, 山东 济南 250021;军事医学研究院生物工程研究所, 北京 100071;首都医科大学附属北京世纪坛医院肿瘤内科 肿瘤治疗性疫苗北京市重点实验室, 北京 100038
基金项目:国家自然科学基金(82072287,32100608)
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heCICs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heCICs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。

关 键 词:异质型细胞叠套结构  肿瘤发生  Ras相关C3肉毒毒素底物1  免疫治疗
收稿时间:2023/2/9 0:00:00

Rac1 promotes the formation of heterotypic cell-in-cell structure
HU Tao,FENG Pengfei,LI Haoyuan,ZHOU Lulin,NIU Zubiao,HUANG Yinuo,WANG Xiaoning,WANG Chenxi,LIU Hui,WU Chengjun.Rac1 promotes the formation of heterotypic cell-in-cell structure[J].Chinese Journal of Biotechnology,2023,39(10):4123-4134.
Authors:HU Tao  FENG Pengfei  LI Haoyuan  ZHOU Lulin  NIU Zubiao  HUANG Yinuo  WANG Xiaoning  WANG Chenxi  LIU Hui  WU Chengjun
Institution:School of Biomedical Engineering, Dalian University of Technology, Dalian 116024, Liaoning, China;Beijing Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, 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;Beijing Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China;Department of Geriatric Hematology and Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China;Beijing Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, China;Beijing Key Laboratory of Therapeutics Vaccines, Department of Oncology, Beijing Shijitan Hospital of Capital Medical University, Beijing 100038, China
Abstract: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.
Keywords:heterotypic cell-in-cell structure  tumorigenesis  Ras-related C3 botulinum toxin substrate 1  immunotherapy
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