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Tumor Biology

, Volume 37, Issue 3, pp 3227–3235 | Cite as

Exosomes from adriamycin-resistant breast cancer cells transmit drug resistance partly by delivering miR-222

  • Dan-dan Yu
  • Ying Wu
  • Xiao-hui Zhang
  • Meng-meng Lv
  • Wei-xian Chen
  • Xiu Chen
  • Su-jin Yang
  • Hongyu Shen
  • Shan-liang Zhong
  • Jin-hai TangEmail author
  • Jian-hua ZhaoEmail author
Original Article

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.

Keywords

Breast cancer Exosome Drug resistance LNA-ELF-FISH 

Notes

Acknowledgments

We thank Shan-Liang Zhong, MD, and Wei-Xian Chen, PhD for their help in discussion and revision.

Compliance with ethical standards

Conflicts of interest

None

Funding

This study was supported by the National Natural Science Foundation of China (81272470). The funders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Dan-dan Yu
    • 1
    • 2
  • Ying Wu
    • 1
  • Xiao-hui Zhang
    • 3
  • Meng-meng Lv
    • 1
    • 2
  • Wei-xian Chen
    • 1
    • 2
  • Xiu Chen
    • 2
  • Su-jin Yang
    • 2
  • Hongyu Shen
    • 2
  • Shan-liang Zhong
    • 3
  • Jin-hai Tang
    • 2
    • 4
    Email author
  • Jian-hua Zhao
    • 3
    • 4
    Email author
  1. 1.The First Clinical School of Nanjing Medical UniversityNanjingChina
  2. 2.Department of General Surgery, Cancer Institute of Jiangsu ProvinceNanjing Medical University Affiliated Cancer HospitalNanjingChina
  3. 3.Center of Clinical Laboratory, Cancer Institute of Jiangsu ProvinceNanjing Medical University Affiliated Cancer HospitalNanjingChina
  4. 4.NanjingChina

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