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- Title
NTERA-2 cells as a model for studying cancer stem cells.
- Authors
Yang, S.; Lin, G.; Deng, L. Y.; Jiang, X. L.; Du, L. L.; Zhou, D.; Yuan, D.; Sun, Y.; Lu, G. X.
- Abstract
Introduction: Embryonal carcinoma cells (NTERA-2) are pluripotent stem cells derived from teratocarcinoma and are considered to be the malignant counterparts of human embryonic cells. As there are few reliable experimental systems available to study the molecular mechanisms governing tumorigenesis, we compared systematically the NTERA-2 and embryonic stem cells and found some characteristics of stem cell and tumorigenesis. The NTERA-2 with characteristics of stem cell and tumour may provide a robust and simple model to study certain aspects of cellular transformation and tumorigenesis in the embryonic phase. Materials/Methods: The markers and pluripotent gene expression of human embryonic stem (HES) cells and were detected by immunocytochemistry and RT-PCR. The differentiation capacity was evaluated by transplantation of HES cells and embryonal carcinoma cells into NOD-SCID mice and the rate of the apoptosis and the cell cycle distribution were detected by the FACS. The gene profile between the embryonic carcinoma cells and embryonic stem cells were compared by the affymetrix gene chip. The analysis of signal pathways in different genes was performed by the Dchip2004 software. The results of the gene chips in the experiments were verified by real-time PCR. Results: The NTERA-2 cells presented expressed the special markers of stem cells, such as Oct-4, Nanog, Sox-2, TERF1, TERF2, REX, FGF4, Cripto, Thy1, LEFTYA and had alkaline phosphatase and telomerase activity. and it could generate cell aggregates similar to embryoid bodies in embryonic stem cells. The NTERA-2 cells can be induced into three germ layers in vitro and in vivo. The more disordered tissue structures existed in the tumour formed by NTERA-2 cells in vivo compared with human embryonic stem cells. The results of the cell cycle analysis showed that the NTERA-2 cells of S phase (63.1 ± 1.27%) was more than the HES cells (35.1 ± 1.4%). The analysis of apoptosis showed the NTERA-2 cells had stronger anti-apoptosis ability. The microarray analysis and real-time PCR results showed that some oncogenes were up-regulated in the NTERA-2 cells, whereas the genes related to differentiation were down-regulated, and that Wnt signal pathway was activated. Conclusions: The NTERA-2 cells had characteristics of stem cells and malignant tumour during expansion and differentiation, In the sense, the NTERA-2 cells were one type of cancer stem cell. The difference between human embryonic stem cells and embryonal carcinoma cells (NTERA-2) may provide a valuable insight into cancer stem cells derived from the embryonic phase.
- Subjects
CANCER cells; EMBRYONIC stem cells
- Publication
Reproductive BioMedicine Online (Reproductive Healthcare Limited), 2008, Vol 16, Issue S2, pS-34
- ISSN
1472-6483
- Publication type
Abstract
- DOI
10.1016/S1472-6483(10)61550-7