PMID- 26432333 OWN - NLM STAT- MEDLINE DCOM- 20170210 LR - 20220409 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 37 IP - 3 DP - 2016 Mar TI - Exosomes from adriamycin-resistant breast cancer cells transmit drug resistance partly by delivering miR-222. PG - 3227-35 LID - 10.1007/s13277-015-4161-0 [doi] AB - 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. FAU - Yu, Dan-Dan AU - Yu DD AD - The First Clinical School of Nanjing Medical University, Nanjing, China. AD - Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Wu, Ying AU - Wu Y AD - The First Clinical School of Nanjing Medical University, Nanjing, China. FAU - Zhang, Xiao-Hui AU - Zhang XH AD - Center of Clinical Laboratory, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Lv, Meng-Meng AU - Lv MM AD - The First Clinical School of Nanjing Medical University, Nanjing, China. AD - Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Chen, Wei-Xian AU - Chen WX AD - The First Clinical School of Nanjing Medical University, Nanjing, China. AD - Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Chen, Xiu AU - Chen X AD - Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Yang, Su-Jin AU - Yang SJ AD - Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Shen, Hongyu AU - Shen H AD - Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Zhong, Shan-Liang AU - Zhong SL AD - Center of Clinical Laboratory, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. FAU - Tang, Jin-Hai AU - Tang JH AD - Department of General Surgery, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. njmu_jhtang@163.com. AD - , Baiziting 42, Nanjing, 210009, China. njmu_jhtang@163.com. FAU - Zhao, Jian-Hua AU - Zhao JH AD - Center of Clinical Laboratory, Cancer Institute of Jiangsu Province, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, China. jhzhaolcjy@126.com. AD - , Baiziting 42, Nanjing, 210009, China. jhzhaolcjy@126.com. LA - eng PT - Journal Article DEP - 20151002 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (MIRN222 microRNA, human) RN - 0 (MicroRNAs) RN - 80168379AG (Doxorubicin) SB - IM MH - Antibiotics, Antineoplastic/pharmacology MH - Apoptosis/drug effects/genetics MH - Breast Neoplasms/genetics/pathology MH - Cell Survival/drug effects/genetics MH - Doxorubicin/*pharmacology MH - Drug Resistance, Neoplasm/*drug effects/genetics MH - Exosomes/*genetics/ultrastructure MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - In Situ Hybridization, Fluorescence MH - MCF-7 Cells MH - MicroRNAs/*genetics MH - Microscopy, Electron, Transmission MH - Microscopy, Fluorescence OTO - NOTNLM OT - Breast cancer OT - Drug resistance OT - Exosome OT - LNA-ELF-FISH EDAT- 2015/10/04 06:00 MHDA- 2017/02/12 06:00 CRDT- 2015/10/04 06:00 PHST- 2015/06/15 00:00 [received] PHST- 2015/09/27 00:00 [accepted] PHST- 2015/10/04 06:00 [entrez] PHST- 2015/10/04 06:00 [pubmed] PHST- 2017/02/12 06:00 [medline] AID - 10.1007/s13277-015-4161-0 [pii] AID - 10.1007/s13277-015-4161-0 [doi] PST - ppublish SO - Tumour Biol. 2016 Mar;37(3):3227-35. doi: 10.1007/s13277-015-4161-0. Epub 2015 Oct 2.