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  • Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling

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    Author(s)
    Endaya, Berwini
    Guan, Shou P.
    Newman, Jennifer P.
    Huynh, Hung
    Sia, Kian C.
    Chong, Siao T.
    Kok, Catherine Y. L.
    Chung, Alexander Y. F.
    Liu, Bin B.
    Hui, Kam Man
    Lam, Paula Y. P.
    Griffith University Author(s)
    Endaya, Berwini
    Year published
    2017
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    Abstract
    The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein that is regarded as one of the markers for tumor initiating cells (TIC) in human hepatocellular carcinoma (HCC). Much work has been directed towards targeting these TICs as a mean of placing these master regulators of cell proliferation and drug resistance under control. Human bone marrow-derived mesenchymal stem cells are known to exhibit an innate property of tumor tropism. However, the possible relationship between MSC and TIC is not well understood. In this study, we show that MSC migration to HCC can be effectively inhibited by TACE and ...
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    The epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein that is regarded as one of the markers for tumor initiating cells (TIC) in human hepatocellular carcinoma (HCC). Much work has been directed towards targeting these TICs as a mean of placing these master regulators of cell proliferation and drug resistance under control. Human bone marrow-derived mesenchymal stem cells are known to exhibit an innate property of tumor tropism. However, the possible relationship between MSC and TIC is not well understood. In this study, we show that MSC migration to HCC can be effectively inhibited by TACE and γ-secretase inhibitors that stop the activation of EpCAM signaling event. Silencing of EpCAM expression through siRNA and antibody approaches also resulted in impaired MSC migration. By contrast, increase levels of EpICD proteins in HCC cells and HCC mouse xenografts resulted in enhanced MSC migration. Taken together, these findings show that MSC is drawn to the more oncogenic population of HCC, and could potentially serve as a cell-based carrier of therapeutic genes to target EpICD-enriched hepatic tumor cells.
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    Journal Title
    Oncotarget
    Volume
    8
    Issue
    33
    DOI
    https://doi.org/10.18632/oncotarget.17633
    Copyright Statement
    © The Author(s) 2017. This is an Open Access article distributed under the terms of the Creative Commons Attribution 3.0 Unported (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Oncology and carcinogenesis
    Oncology and carcinogenesis not elsewhere classified
    Publication URI
    http://hdl.handle.net/10072/368589
    Collection
    • Journal articles

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