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Drug-resistant breast cancer cell line displays cancer stem cell phenotype and responds sensitively to epigenetic drug SAHA

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Abstract

Cancer stem cell (CSC) population in solid human breast tumor is identified by CD44+/CD24− phenotype, characterized by high tumorigenicity, invasiveness, and drug resistance. In this study, we characterized drug-resistant breast cancer cell line-MCF-7/Adr and a number of other breast cancer cell lines using flow cytometry, immunofluorescence, mammosphere formation assay, and migration assay, examining their CSC immunophenotypes, presence of CSC proteins, tumorigenicity in vitro, and migratory rates, respectively. Our results show that MCF-7/Adr cells uniformly display CSC characteristics yet retain low migratory rate. They are also able to self-renew and differentiate under floating culture conditions. Furthermore, MCF-7/Adr is selectively sensitive to epigenetic drug, suberoylanilide hydroxamic acid, losing drug resistance and changes morphology yet retaining CSC immunophenotypes. In conclusion, we show that resistant breast cancer cell line MCF-7/Adr demonstrates uniform CSC-like characteristics and are sensitive to epigenetic drug treatment.

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Abbreviations

BCSC:

Breast cancer stem cell

SAHA:

Suberoylanilide hydroxamic acid

hMSC:

Human mesenchymal stem cell

ESA:

Epithelial-specific antigen

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Acknowledgment

This study was funded by grant R01 CA149359-03 (to VL) from the National Cancer Institute of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA

    Shan Lu & Vinod Labhasetwar

  2. Integrated Bioscience Program, University of Akron, Akron, OH, 44325, USA

    Shan Lu

  3. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, 44195, USA

    Vinod Labhasetwar

  4. Department of Biomedical Engineering/ND20, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Vinod Labhasetwar

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  1. Shan Lu
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  2. Vinod Labhasetwar
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Correspondence to Vinod Labhasetwar.

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Lu, S., Labhasetwar, V. Drug-resistant breast cancer cell line displays cancer stem cell phenotype and responds sensitively to epigenetic drug SAHA. Drug Deliv. and Transl. Res. 3, 183–194 (2013). https://doi.org/10.1007/s13346-012-0113-z

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  • DOI: https://doi.org/10.1007/s13346-012-0113-z

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