title: Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs.
abstract: While adriamycin (adr) offers improvement in survival for breast cancer (BCa) patients, unfortunately, drug resistance is almost inevitable. Mounting evidence suggests that exosomes act as a vehicle for genetic cargo and constantly shuttle biologically active molecules including microRNAs (miRNAs) between heterogeneous populations of tumor cells, engendering a resistance-promoting niche for cancer progression. Our recent study showed that exosomes from docetaxel-resistance BCa cells could modulate chemosensitivity by delivering miRNAs. Herein, we expand on our previous finding and explore the relevance of exosome-mediated miRNA delivery in resistance transmission of adr-resistant BCa sublines. We now demonstrated the selective packing of miRNAs within the exosomes (A/exo) derived from adr-resistant BCa cells. The highly expressed miRNAs in A/exo were significantly increased in recipient fluorescent sensitive cells (GFP-S) after A/exo incorporation. Gene ontology analysis of predicted targets showed that the top 30 most abundant miRNAs in A/exo were involved in crucial biological processes. Moreover, A/exo not only loaded miRNAs for its production and release but also carried miRNAs associated with Wnt signaling pathway. Furthermore, A/exo co-culture assays indicated that miRNA-containing A/exo was able to increase the overall resistance of GFP-S to adr exposure and regulate gene levels in GFP-S. Our results reinforce our earlier reports that adr-resistant BCa cells could manipulate a more deleterious microenvironment and transmit resistance capacity through altering gene expressions in sensitive cells by transferring specific miRNAs contained within exosomes.
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, China.|Department of Thyroid and Breast Surgery, Huai'an Second People's Hospital, Huai'an, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Mao
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, China.|Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, China.|Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Wei-Xian
authors.initials: WX
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Huai'an First People's Hospital, Huai'an, China.
authors.forename: Yan-Qin
authors.initials: YQ
authors.lastname: Cai
authors.affiliation: The Fourth Clinical School of Nanjing Medical University, Nanjing, China.|Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yu
authors.affiliation: Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Shan-Liang
authors.initials: SL
authors.lastname: Zhong
authors.affiliation: Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhao
authors.affiliation: Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China. momopannj@sina.com.|, 42 Baiziting, Nanjing, China. momopannj@sina.com.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China. jhtangnj@126.com.|, 42 Baiziting, Nanjing, China. jhtangnj@126.com.
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018920:Coculture Techniques; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D055354:Exosomes / Q000187:drug effects / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D043823:Taxoids / Q000008:administration & dosage; D059016:Tumor Microenvironment / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin
keywords: Adriamycin; Breast cancer; Chemotherapy; Drug resistance; Exosomes; MicroRNAs