Oncotarget

Research Papers:

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

Berwini Endaya, Shou P. Guan, Jennifer P. Newman, Hung Huynh, Kian C. Sia, Siao T. Chong, Catherine Y.L. Kok, Alexander Y.F. Chung, Bin B. Liu, Kam M. Hui and Paula Y.P. Lam _

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Oncotarget. 2017; 8:54629-54639. https://doi.org/10.18632/oncotarget.17633

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Abstract

Berwini Endaya1,2,*, Shou P. Guan1,*, Jennifer P. Newman1, Hung Huynh1, Kian C. Sia1, Siao T. Chong1, Catherine Y.L. Kok1, Alexander Y.F. Chung3, Bin B. Liu4, Kam M. Hui6,7,8 and Paula Y.P. Lam1,5,8

1Division of Cellular and Molecular Research, National Cancer Centre, Singapore City, Singapore

2Griffith Health Institute, Griffith University, Southport, Australia

3Department of General Surgery, Singapore General Hospital, Singapore City, Singapore

4Liver Cancer Institute of Fudan University, Shanghai, China

5Department of Physiology, National University of Singapore, Singapore City, Singapore

6Department of Biochemistry, National University of Singapore, Singapore City, Singapore

7Institute of Molecular and Cell Biology, A*STAR, Singapore City, Singapore

8Cancer and Stem Cells Biology Program, Duke-NUS Graduate Medical School, Singapore City, Singapore

*These authors are considered as co-first authors

Correspondence to:

Paula Y.P. Lam, email: [email protected]

Keywords: human bone marrow-derived MSC, tumor tropism, EpCAM signaling, human hepatocellular carcinoma

Received: September 16, 2016     Accepted: February 27, 2017     Published: May 05, 2017

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 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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