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Tumor Biology

, Volume 35, Issue 10, pp 9649–9659 | Cite as

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

  • Wei-xian Chen
  • Yan-qin Cai
  • Meng-meng Lv
  • Lin Chen
  • Shan-liang Zhong
  • Teng-fei Ma
  • Jian-hua ZhaoEmail author
  • Jin-hai TangEmail author
Research Article

Abstract

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.

Keywords

Exosomes Drug resistance Breast cancer MicroRNAs Docetaxel Chemotherapy 

Notes

Acknowledgments

We would like to acknowledge the funding body for supporting this work: the National Natural Science Foundation of China provided to Jin-hai Tang (81272470). We also thank Jun Zhang, Hao Ji, and Xiao-hui Zhang for their discussion and help in our manuscript.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Wei-xian Chen
    • 1
    • 2
  • Yan-qin Cai
    • 3
  • Meng-meng Lv
    • 1
    • 2
  • Lin Chen
    • 2
    • 4
  • Shan-liang Zhong
    • 5
  • Teng-fei Ma
    • 1
    • 5
  • Jian-hua Zhao
    • 5
    Email author
  • Jin-hai Tang
    • 2
    Email author
  1. 1.The Fourth Clinical SchoolNanjing Medical UniversityNanjingChina
  2. 2.Department of General SurgeryNanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu ProvinceNanjingChina
  3. 3.Department of Thoracic SurgeryNanjing Medical University Affiliated Huai’an First People’s HospitalHuai’anChina
  4. 4.Graduate SchoolXuzhou Medical CollegeXuzhouChina
  5. 5.Center of Clinical LaboratoryNanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu ProvinceNanjingChina

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