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Title: Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling
Authors: Endaya B 
Guan S.P. 
Newman J.P.
Huynh H. 
Sia K.C.
Chong S.T.
Kok C.Y.L.
Chung A.Y.F. 
Liu B.B.
Hui K.M.
Lam P.Y.P. 
Keywords: epithelial cell adhesion molecule
gamma secretase inhibitor
small interfering RNA
tumor necrosis factor alpha converting enzyme inhibitor
animal experiment
animal model
animal tissue
cell migration
controlled study
hepatocellular carcinoma cell line
human cell
human tissue
liver carcinogenesis
liver cell carcinoma
mesenchymal stem cell
protein expression
signal transduction
tumor xenograft
Issue Date: 2017
Publisher: Impact Journals LLC
Citation: Endaya B, Guan S.P., Newman J.P., Huynh H., Sia K.C., Chong S.T., Kok C.Y.L., Chung A.Y.F., Liu B.B., Hui K.M., Lam P.Y.P. (2017). Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling. Oncotarget 8 (33) : 54629-54639. ScholarBank@NUS Repository.
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 ?-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. © Endaya et al.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.17633
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