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  • Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells

    Author(s)
    Santisteban, Marta
    Reiman, Jennifer M.
    Asiedu, Michael K.
    Behrens, Marshall D.
    Nassar, Aziza
    Kalli, Kimberly R.
    Haluska, Paul
    Ingle, James N.
    Hartmann, Lynn C.
    Manjili, Masoud H.
    Radisky, Derek
    Ferrone, Soldano
    Knutson, Keith
    Griffith University Author(s)
    Reiman, Jennifer M.
    Year published
    2009
    Metadata
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    Abstract
    The breast cancer stem cell (BCSC) hypotheses suggest that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source of these cells is unclear. We previously observed that induction of an immune response against an epithelial breast cancer led in vivo to the T-cell-dependent outgrowth of a tumor, the cells of which had undergone epithelial to mesenchymal transition (EMT). The resulting mesenchymal tumor cells had a CD24-/loCD44+ phenotype, consistent with BCSCs. In the present study, we found that EMT was induced by CD8 T cells and the resulting tumors had characteristics of BCSCs, ...
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    The breast cancer stem cell (BCSC) hypotheses suggest that breast cancer is derived from a single tumor-initiating cell with stem-like properties, but the source of these cells is unclear. We previously observed that induction of an immune response against an epithelial breast cancer led in vivo to the T-cell-dependent outgrowth of a tumor, the cells of which had undergone epithelial to mesenchymal transition (EMT). The resulting mesenchymal tumor cells had a CD24-/loCD44+ phenotype, consistent with BCSCs. In the present study, we found that EMT was induced by CD8 T cells and the resulting tumors had characteristics of BCSCs, including potent tumorigenicity, ability to reestablish an epithelial tumor, and enhanced resistance to drugs and radiation. In contrast to the hierarchal cancer stem cell hypothesis, which suggests that breast cancer arises from the transformation of a resident tissue stem cell, our results show that EMT can produce the BCSC phenotype. These findings have several important implications related to disease progression and relapse.
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    Journal Title
    Cancer Research
    Volume
    69
    Issue
    7
    DOI
    https://doi.org/10.1158/0008-5472.CAN-08-3343
    Subject
    Tumour Immunology
    Oncology and Carcinogenesis
    Publication URI
    http://hdl.handle.net/10072/37894
    Collection
    • Journal articles

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