title: Exosomes from adriamycin-resistant breast cancer cells transmit drug resistance partly by delivering miR-222.
abstract: Breast cancer (BCa) is one of the major deadly cancers in women. However, treatment of BCa is still hindered by the acquired-drug resistance. It is increasingly reported that exosomes take part in the development, metastasis, and drug resistance of BCa. However, the specific role of exosomes in drug resistance of BCa is poorly understood. In this study, we investigate whether exosomes transmit drug resistance through delivering miR-222. We established an adriamycin-resistant variant of Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line (MCF-7/Adr) from a drug-sensitive variant (MCF-7/S). Exosomes were isolated from cell supernatant by ultracentrifugation. Cell viability was assessed by MTT assay and apoptosis assay. Individual miR-222 molecules in BCa cells were detected by fluorescence in situ hybridization (FISH). Then, FISH was combined with locked nucleic acid probes and enzyme-labeled fluorescence (LNA-ELF-FISH). Individual miR-222 could be detected as bright photostable fluorescent spots and then the quantity of miR-222 per cell could be counted. Stained exosomes were taken in by the receipt cells. MCF-7/S acquired drug resistance after co-culture with exosomes from MCF-7/Adr (A/exo) but did not after co-culture with exosomes from MCF-7/S (S/exo). The quantity of miR-222 in A/exo-treated MCF-7/S was significantly greater than in S/exo-treated MCF-7/S. MCF-7/S transfected with miR-222 mimics acquired adriamycin resistance while MCF-7/S transfected with miR-222 inhibitors lost resistance. In conclusion, exosomes are effective in transmitting drug resistance and the delivery of miR-222 via exosomes may be a mechanism.
authors.affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.|Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yu
authors.affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Center of Clinical Laboratory, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.|Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Lv
authors.affiliation: The First Clinical School of Nanjing Medical University, Nanjing, China.|Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Wei-Xian
authors.initials: WX
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Shen
authors.affiliation: Center of Clinical Laboratory, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China.
authors.forename: Shan-Liang
authors.initials: SL
authors.lastname: Zhong
authors.affiliation: Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. njmu_jhtang@163.com.|, Baiziting 42, Nanjing, 210009, China. njmu_jhtang@163.com.
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Tang
authors.affiliation: Center of Clinical Laboratory, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. jhzhaolcjy@126.com.|, Baiziting 42, Nanjing, 210009, China. jhzhaolcjy@126.com.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D055354:Exosomes / Q000235:genetics* / Q000648:ultrastructure; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence
chemical_list: D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D035683:MicroRNAs; C525710:MIR222, human
keywords: Breast cancer; Drug resistance; Exosome; LNA-ELF-FISH