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    Doxorubicin fails to eradicate cancer stem cells derived from anaplastic thyroid carcinoma cells: characterization of resistant cells.

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    Authors
    Zheng, Xuqin
    Cui, Dai
    Xu, Shuhang
    Brabant, Georg E
    Derwahl, Michael
    Affiliation
    Division of Endocrinology, Department of Medicine, St Hedwig Hospital and Humboldt University, D-10115 Berlin, Berlin, Germany.
    Issue Date
    2010-08
    
    Metadata
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    Abstract
    Current chemotherapy with doxorubicin fails to eradicate anaplastic thyroid cancer or even to stop tumor progress which may be due to the failure of these drugs to effectively target putative cancer stem cells. To test this hypothesis, anaplastic thyroid cell lines were characterized by FACS for their content of cancer stem cells, their in vitro sphere-forming capacity and their expression of multidrug resistance transporters of the ABC gene family which may confer drug resistance to the cells. Cells were treated with doxorubicin in short-term and long-term culture up to 6 months to establish a resistant cell line. The survival of cancer and cancer stem cells and the differential expression of transporters were analyzed. Anaplastic thyroid cancer cell lines that consisted of 0.4-0.8% side population cells, expressed ABCG2 and multi-drug-resistant 1 (MDR1) transporters. Treatment with doxorubicin gradually killed the non-side population of cancer cells derived from anaplastic thyroid carcinoma cells. This conferred a growth advantage to cancer stem cells which in turn overgrew the culture. Resistant cell line consisted of a 70% side population fraction enriched with Oct4-positive cancer stem cells. Inhibition of ABCG2 and/or MDR1 revealed that resistance of cancer stem cells to doxorubicin may be mainly due to the expression of these ABC transporters that were highly up-regulated in the resistant subline. The poor outcome of chemotherapy with doxorubicin in anaplastic thyroid carcinoma may be partly explained by up-regulation of ABCG2 and MDR1 transporters that confers resistance to cancer stem cells. Thus an effective treatment of anaplastic thyroid cancer has not only to destroy cancer cells that represent the bulk of tumor cell population but also cancer stem cells that may drive tumor progression.
    Citation
    Doxorubicin fails to eradicate cancer stem cells derived from anaplastic thyroid carcinoma cells: characterization of resistant cells. 2010, 37 (2):307-15 Int J Oncol
    Journal
    International Journal of Oncology
    URI
    http://hdl.handle.net/10541/111118
    DOI
    10.3892/ijo_00000679
    PubMed ID
    20596658
    Type
    Article
    Language
    en
    ISSN
    1791-2423
    ae974a485f413a2113503eed53cd6c53
    10.3892/ijo_00000679
    Scopus Count
    Collections
    All Christie Publications
    Endocrinology

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