Abstract
Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immunodeficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.
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Acknowledgements
The relevant institutional Ethics Committees approved this study. We thank the participants and their families for their kind cooperation, generosity, and patience. This work was supported by the project of National Basic Research Program of China (2007CB947802, 2009CB941200).
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( Supplementary information is linked to the online version of the paper on the Cell Research website.)
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Supplementary information, Figure S1
Spheres were cultured without serum and detected by specific antibodies against gastrin, mucin, CD44, or Ki67 antigens. (PDF 164 kb)
Supplementary information, Figure S2
An example shows FACS analysis of immunopheotypes of the cells obtained from tumor tissues of human patients. (PDF 197 kb)
Supplementary information, Figure S3
An example of FACS analysis of immunphenotypes of the cells obtained from tissue and blood samples of normal individuals and GAC patients. (PDF 275 kb)
Supplementary information, Table S1
Tumorigenic capacity of different cell subpopulations (PDF 948 kb)
Supplementary information, Table S2
Viability of both unsorted cells and sorted CD44+/CD54+ cells before injecting into mice (PDF 1061 kb)
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Chen, T., Yang, K., Yu, J. et al. Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients. Cell Res 22, 248–258 (2012). https://doi.org/10.1038/cr.2011.109
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DOI: https://doi.org/10.1038/cr.2011.109
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