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

• Published in: Cell research Vol. 26; no. 6; pp. 713 - 727
• Main Authors: Ma, Jingwei, Zhang, Yi, Tang, Ke, Zhang, Huafeng, Yin, Xiaonan, Li, Yong, Xu, Pingwei, Sun, Yanling, Ma, Ruihua, Ji, Tiantian, Chen, Junwei, Zhang, Shuang, Zhang, Tianzhen, Luo, Shunqun, Jin, Yang, Luo, Xiuli, Li, Chengyin, Gong, Hongwei, Long, Zhixiong, Lu, Jinzhi, Hu, Zhuowei, Cao, Xuetao, Wang, Ning, Yang, Xiangliang, Huang, Bo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2016; Nature Publishing Group
• Subjects: 631/61/51; 631/61/54; 631/67/1059/2326; 631/67/1059/99; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biomedical and Life Sciences; Cell Biology; Cell Line, Tumor; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell-Derived Microparticles - metabolism; Doxorubicin - pharmacology; Drug resistance; Drug Resistance, Neoplasm - drug effects; Humans; Life Sciences; Mice, Inbred BALB C; Microtubules - drug effects; Microtubules - metabolism; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Original; original-article; Pleural Effusion - pathology; Soft Tissue Neoplasms - drug therapy; Soft Tissue Neoplasms - pathology; Stem cells; Survival Analysis; Tumors; 临床应用; 化疗药物; 微粒; 抗肿瘤药物; 组织重建; 耐药; 肿瘤细胞; 逆转; drug resistance; nuclear delivery; tumor-repopulating cells; drug-packaging microparticles
• ISSN: 1001-0602; 1748-7838
• DOI: 10.1038/cr.2016.53

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 microparficles （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 tu- mor cell softness in uptake of T-MPs and effectiveness of a novel approach in reversing drug resistance of TRCs with promising clinical applications.