Transforming growth factor-β1-induced epithelial-mesenchymal transition generates ALDH-positive cells with stem cell properties in cholangiocarcinoma
| Autor: | Yong cheng Liu, Shengping Li, Xiang-Ming Lao, Jing Xu, Guohe Lin, Wen Chao Wu, Limin Zheng, Ze Yu Shuang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Cancer Research Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Aldehyde dehydrogenase Mice SCID Metastasis Cholangiocarcinoma Transforming Growth Factor beta1 Mice Cancer stem cell Mice Inbred NOD Cell Line Tumor medicine Animals Humans Epithelial–mesenchymal transition biology Mesenchymal stem cell Aldehyde Dehydrogenase medicine.disease Bile Ducts Intrahepatic Oncology Bile Duct Neoplasms Cell culture Cancer research biology.protein Neoplastic Stem Cells Stem cell Transforming growth factor |
| Zdroj: | Cancer letters. 354(2) |
| ISSN: | 1872-7980 |
| Popis: | Epithelial-mesenchymal transition (EMT) is a major factor that facilitates the invasiveness and metastasis of cancer. Recent studies have demonstrated that EMT plays a key role in generating cancer stem cells (CSCs). This study aimed to investigate the effect of EMT on CSCs that were identified as positive for aldehyde dehydrogenase (ALDH) in cholangiocarcinoma (CCA). We demonstrated that transforming growth factor-β1 (TGF-β1)-induced EMT in the human cholangiocarcinoma (CCA) cell line, TFK-1, resulted in the acquisition of mesenchymal traits, as well as the expression of ALDH, which was accompanied by decreased sensitivity to the chemotherapeutic agent, 5-fluorouracil. ALDH-positive cells isolated from TFK-1 cells had higher proliferation potential in vitro and tumourigenic ability in vivo. They also expressed mesenchymal markers. Moreover, the expression levels of TGF-β1 and ALDH1 were correlated with poor prognosis in patients. We conclude that ALDH acts as a marker for CSCs in CCA, and TGF-β1-induced EMT is involved in the generation of CSCs. These findings offer a new tool for the study of CCA stem cells and illustrate a direct link between EMT and the gain of stem-cell properties. |
| Databáze: | OpenAIRE |
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