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Tumour Biol. 2016 Apr;37(4):5247-56. doi: 10.1007/s13277-015-4402-2. Epub 2015 Nov 10.

Exosomes decrease sensitivity of breast cancer cells to adriamycin by delivering microRNAs.

Mao L1,2, Li J1,3, Chen WX1,3, Cai YQ4, Yu DD1,3, Zhong SL5, Zhao JH5, Zhou JW6,7, Tang JH8,9.

Author information

1
The Fourth Clinical School of Nanjing Medical University, Nanjing, China.
2
Department of Thyroid and Breast Surgery, Huai'an Second People's Hospital, Huai'an, China.
3
Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
4
Department of Thoracic Surgery, Nanjing Medical University Affiliated Huai'an First People's Hospital, Huai'an, China.
5
Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China.
6
Department of Molecular Cell Biology and Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China. momopannj@sina.com.
7
, 42 Baiziting, Nanjing, China. momopannj@sina.com.
8
Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, China. jhtangnj@126.com.
9
, 42 Baiziting, Nanjing, China. jhtangnj@126.com.

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.

KEYWORDS:

Adriamycin; Breast cancer; Chemotherapy; Drug resistance; Exosomes; MicroRNAs

PMID:
26555545
DOI:
10.1007/s13277-015-4402-2
[Indexed for MEDLINE]

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