title: Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles.
abstract: Developing novel approaches to reverse the drug resistance of tumor-repopulating cells (TRCs) or stem cell-like cancer cells is an urgent clinical need to improve outcomes of cancer patients. Here we show an innovative approach that reverses drug resistance of TRCs using tumor cell-derived microparticles (T-MPs) containing anti-tumor drugs. TRCs, by virtue of being more deformable than differentiated cancer cells, preferentially take up T-MPs that release anti-tumor drugs after entering cells, which in turn lead to death of TRCs. The underlying mechanisms include interfering with drug efflux and promoting nuclear entry of the drugs. Our findings demonstrate the importance of tumor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.|Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Ma
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.|Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory for Cell Biomechanics and Regenerative Medicine, Department of Biomedical Engineering, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Pingwei
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Ruihua
authors.initials: R
authors.lastname: Ma
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Ji
authors.affiliation: Laboratory for Cell Biomechanics and Regenerative Medicine, Department of Biomedical Engineering, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory for Cell Biomechanics and Regenerative Medicine, Department of Biomedical Engineering, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Tianzhen
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Shunqun
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Oncology, Hubei Provincial Hospital of TCM, Wuhan, Hubei 430061, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Luo
authors.affiliation: Department of Oncology, Hubei Provincial Hospital of TCM, Wuhan, Hubei 430061, China.
authors.forename: Chengyin
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Oncology, Hubei Provincial Hospital of TCM, Wuhan, Hubei 430061, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gong
authors.affiliation: Department of Oncology, the Fifth Hospital of Wuhan, Wuhan, Hubei 430050, China.
authors.forename: Zhixiong
authors.initials: Z
authors.lastname: Long
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Lu
authors.affiliation: Molecular Immunology and Pharmacology Group, State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Zhuowei
authors.initials: Z
authors.lastname: Hu
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.affiliation: Laboratory for Cell Biomechanics and Regenerative Medicine, Department of Biomedical Engineering, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.|Department of Mechanical Science and Engineering, College of Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.|Department of Biochemistry & Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, Hubei 430030, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D010996:Pleural Effusion / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin