Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles

被引：204

作者：

Ma, Jingwei ^{[1
,2
,3
]}

Zhang, Yi ^{[1
,2
]}

Tang, Ke ^{[1
,2
,3
]}

Zhang, Huafeng ^{[1
,2
]}

Yin, Xiaonan ^{[1
,2
]}

Li, Yong ^{[3
]}

Xu, Pingwei ^{[4
]}

Sun, Yanling ^{[3
]}

Ma, Ruihua ^{[3
]}

Ji, Tiantian ^{[3
]}

Chen, Junwei ^{[4
]}

Zhang, Shuang ^{[4
]}

Zhang, Tianzhen ^{[1
,2
]}

Luo, Shunqun ^{[3
]}

Jin, Yang ^{[5
]}

Luo, Xiuli ^{[6
]}

Li, Chengyin ^{[6
]}

Gong, Hongwei ^{[6
]}

Long, Zhixiong ^{[7
]}

Lu, Jinzhi ^{[1
,2
]}

Hu, Zhuowei ^{[8
]}

Cao, Xuetao ^{[1
,2
]}

Wang, Ning ^{[4
,9
]}

Yang, Xiangliang ^{[10
]}

Huang, Bo ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Med Sci, Inst Basic Med Sci, Natl Key Lab Med Mol Biol, Beijing 100005, Peoples R China

[2] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Immunol, Beijing 100005, Peoples R China

[3] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430030, Hubei, Peoples R China

[4] Huazhong Univ Sci & Technol, Lab Cell Biomech & Regenerat Med, Dept Biomed Engn, Sch Life Sci & Technol, Wuhan 430074, Hubei, Peoples R China

[5] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Resp & Crit Care Med, Key Lab Pulm Dis,Hlth Minist,Union Hosp, Wuhan 430022, Hubei, Peoples R China

[6] Hubei Prov Hosp TCM, Dept Oncol, Wuhan 430061, Hubei, Peoples R China

[7] Fifth Hosp Wuhan, Dept Oncol, Wuhan 430050, Hubei, Peoples R China

[8] Chinese Acad Med Sci, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Mol Immunol & Pharmacol Grp, Beijing 100050, Peoples R China

[9] Univ Illinois, Coll Engn, Dept Mech Sci & Engn, Urbana, IL 61801 USA

[10] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan 430074, Hubei, Peoples R China

来源：

CELL RESEARCH | 2016年 / 26卷 / 06期

基金：

中国国家自然科学基金;

关键词：

tumor-repopulating cells; drug-packaging microparticles; drug resistance; nuclear delivery; CANCER STEM-CELLS; BREAST-CANCER; MICROTUBULES; INHIBITION; MECHANISMS; CHALLENGES; PATHWAYS; DELIVERY; GROWTH;

D O I：

10.1038/cr.2016.53

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：713 / 727

页数：15

共 42 条

[1] Resistance, epigenetics and the cancer ecosystem [J].

Baylin, Stephen B. .

NATURE MEDICINE, 2011, 17 (03) :288-289

[2]

Beningo KA, 2002, J CELL SCI, V115, P849

[3] DNA-Damage Response in Tissue-Specific and Cancer Stem Cells [J].

Blanpain, Cedric ;

Mohrin, Mary ;

Sotiropoulou, Panagiota A. ;

Passegue, Emmanuelle .

CELL STEM CELL, 2011, 8 (01) :16-29

[4] BIOLOGY Three known unknowns [J].

Bourzac, Katherine .

NATURE, 2014, 509 (7502) :S69-S71

[5] Role of the cytoskeleton in nuclear import [J].

Campbell, EA ;

Hope, TJ .

ADVANCED DRUG DELIVERY REVIEWS, 2003, 55 (06) :761-771

[6] The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs [J].

Chen, Lei ;

Xiao, Zhifeng ;

Meng, Yue ;

Zhao, Yannan ;

Han, Jin ;

Su, Guannan ;

Chen, Bing ;

Dai, Jianwu .

BIOMATERIALS, 2012, 33 (05) :1437-1444

[7]

Chowdhury F, 2010, NAT MATER, V9, P82, DOI [10.1038/nmat2563, 10.1038/NMAT2563]

[8] The cancer stem cell: premises, promises and challenges [J].

Clevers, Hans .

NATURE MEDICINE, 2011, 17 (03) :313-319

[9] Nanomechanical analysis of cells from cancer patients [J].

Cross, Sarah E. ;

Jin, Yu-Sheng ;

Rao, Jianyu ;

Gimzewski, James K. .

NATURE NANOTECHNOLOGY, 2007, 2 (12) :780-783

[10] Tumour stem cells and drug resistance [J].

Dean, M ;

Fojo, T ;

Bates, S .

NATURE REVIEWS CANCER, 2005, 5 (04) :275-284

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