Exosomes from docetaxel-resistant breast cancer cells alter chemosensitivity by delivering microRNAs

Breast cancer (BCa) remains chemo-unresponsive by inevitable progression of resistance to first-line treatment with docetaxel (doc). Emerging studies indicate that exosomes act as mediators of intercellular communication between heterogeneous populations of tumor cells, engendering a transmitted dru...

Full description

Saved in:
Bibliographic Details
Published in:Tumor biology 2014-10, Vol.35 (10), p.9649-9659
Main Authors: Chen, Wei-xian, Cai, Yan-qin, Lv, Meng-meng, Chen, Lin, Zhong, Shan-liang, Ma, Teng-fei, Zhao, Jian-hua, Tang, Jin-hai
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Cancer Research
Cell Communication
Cell Line, Tumor
Cells
Chemotherapy
Drug Resistance, Neoplasm - genetics
Drug therapy
Exosomes - metabolism
Humans
MicroRNAs - genetics
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Research Article
Ribonucleic acid
RNA
Sensitivity analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Breast cancer (BCa) remains chemo-unresponsive by inevitable progression of resistance to first-line treatment with docetaxel (doc). Emerging studies indicate that exosomes act as mediators of intercellular communication between heterogeneous populations of tumor cells, engendering a transmitted drug resistance for cancer development. Such modulatory effects have been related to the constant shuttle of biologically active molecules including microRNAs (miRNAs). Here, we aimed to investigate the relevance of exosome-mediated miRNA delivery in resistance transmission of BCa subpopulations. Using microarray and polymerase chain reaction, we found that exosomes from doc-resistant BCa cells (D/exo) loaded cellular miRNAs. Following D/exo transfer to the fluorescent sensitive cells (GFP-S), some miRNAs were significantly increased in recipient GFP-S. Target gene prediction and pathway analysis revealed the involvement of the top 20 most abundant miRNAs of D/exo in pathways implicated in therapy failure. Coculture assays showed that miRNA-containing D/exo increased the overall resistance of GFP-S to doc exposure. Moreover, D/exo was able to alter gene expression in GFP-S. Our results open up an intriguing possibility that drug-resistant BCa cells may spread chemoresistance to sensitive ones by releasing exosomes and that the effects could be partly attributed to the intercellular transfer of specific miRNAs.
ISSN:1010-4283
1423-0380
DOI:10.1007/s13277-014-2242-0