Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling
| Autor: | Shou P. Guan, Kam M. Hui, Kian Chuan Sia, Siao T. Chong, Alexander Y. F. Chung, Berwini Endaya, Catherine Y. L. Kok, Jennifer P. Newman, Bin B. Liu, Paula Y.P. Lam, Hung Huynh |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
EpCAM signaling Cell Population 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine human hepatocellular carcinoma medicine Gene silencing education education.field_of_study biology Cell growth business.industry Mesenchymal stem cell Epithelial cell adhesion molecule medicine.disease human bone marrow-derived MSC 030104 developmental biology medicine.anatomical_structure Oncology chemistry 030220 oncology & carcinogenesis Hepatocellular carcinoma Immunology biology.protein Cancer research tumor tropism Antibody business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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