Human circulating and tissue gastric cancer stem cells display distinct epithelial–mesenchymal features and behaviors
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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.
Methods and Results
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.
KeywordsMetastasis Cancer stem cells Mesenchymal Self-renewal Proliferative capabilities Apoptosis
The relevant institutional Ethics Committees approved this study. We thank the participants and their families for their kind cooperation, generosity, and patience.
This study was funded by National High-tech R&D Program (863 Program), No. 2015AA020306, the project of National Basic Research Program of China (to X.M. 2015CB942800), the Nature Science Foundation of China (to X.M. 81361120381. To C.F. 81402446. To T.C, 81201683 and 81672904).
Compliance with ethical standards
Conflict of interest
All authors declare that he/she has no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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