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Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589609/ https://www.ncbi.nlm.nih.gov/pubmed/28903370 http://dx.doi.org/10.18632/oncotarget.17633 |
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author | 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 M. Lam, Paula Y.P. |
author_facet | 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 M. Lam, Paula Y.P. |
author_sort | Endaya, Berwini |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5589609 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55896092017-09-12 Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling 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 M. Lam, Paula Y.P. Oncotarget Research Paper 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. Impact Journals LLC 2017-05-05 /pmc/articles/PMC5589609/ /pubmed/28903370 http://dx.doi.org/10.18632/oncotarget.17633 Text en Copyright: © 2017 Endaya et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper 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 M. Lam, Paula Y.P. Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling |
title | Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling |
title_full | Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling |
title_fullStr | Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling |
title_full_unstemmed | Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling |
title_short | Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling |
title_sort | human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated epcam signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589609/ https://www.ncbi.nlm.nih.gov/pubmed/28903370 http://dx.doi.org/10.18632/oncotarget.17633 |
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