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Human circulating and tissue gastric cancer stem cells display distinct epithelial-mesenchymal features and behaviors.

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机构: [1]Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China [2]Health Science Center, Institute of Molecular Medicine, Shenzhen University, Shenzhen 518060, China [3]Department of Gastrointestinal Surgery and Institute of Digestive Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China [4]Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China
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关键词: Metastasis Cancer stem cells Mesenchymal Self-renewal Proliferative capabilities Apoptosis

摘要:
Metastasis is a leading cause of cancer-related-deaths worldwide. Recently, cancer stem cells (CSCs) have been believed to be responsible for tumor initiation and metastasis, but till now, difference of cellular features and behaviors between CSCs from tumor tissues (TCSCs) and circulation (CCSCs) remains largely unknown, which hinders the progression of targeted therapies for metastasis. Here, we provide the features of circulating gastric cancer stem cells (CGCSCs) isolated from human gastric adenocarcinoma. The CGCSCs and TGCSCs were culture in a same serum free stem cell culture medium, however the morphology are different with each other. EMT-associated markers were measured by Immunofluorescence, Western Blotting, and RT-PCR methods, and the results indicated that the CGCSCs and TGCSCs carry different epithelial-mesenchymal features. And then, proliferation and apoptosis assays revealed that the CGCSCs exhibited characteristics of higher proliferation and resistance to apoptosis in vitro. Soft agar assay and nude mice tumorigenicity assay displayed strong tumorigenicity of CGCSCs. Finally, Matrigel invasion assays and in vivo experimental metastasis assay were also performed, which demonstrated that CGCSCs carry high invasive and metastatic capabilities than TGCSCs. As expected, the CGCSCs indeed showed extremely invasive and metastatic properties. They also exhibited distinctive mesenchymal phenotypes, high self-renewal, proliferative capabilities, tumor induction and low apoptosis. Interestingly, CGCSCs show small cell-size than TGCSCs (tissue gastric cancer stem cells). The findings might help us to understand the biological characteristic of CGCSCs deeply, and give light to strategies for cancer therapies.

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出版当年[2017]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
最新[2023]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学
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第一作者机构: [1]Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China
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通讯机构: [4]Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China
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