Tumourigenic characteristics of embryonal carcinoma cells as a model for studying tumour progression of human embryonic stem cells.
OBJECTIVE
The objective of this study was to compare tumourigenic characteristics of human embryonic stem cells (HESCs) and embryonal carcinoma cells (ECCs) to identify a robust and simple model for studying certain aspects of cell transformation and tumourigenesis, in tumour progression of HESCs.


METHODS
SSEA-3 positive ECCs (NTERA-2) cells were identified and compared to HESCs (ch HES-20) in terms of pluripotency and differentiation capacity, growth characteristics, gene expression profiles and signalling pathways.


RESULTS
Our results showed that NTERA-2 cells shared similarities in expression markers of pluripotency to ch HES-20 cells. However, NTERA-2 cells also expressed some markers of differentiation and had a tendency to differentiate towards ectodermal endpoints. We identified NTERA-2 cells with higher S-phase fraction in cell cycle distribution, anti-apoptosis markers and robust self-renewal ability, compared to ch HES-20 cells. Microarray analysis and real-time PCR results showed that some oncogenes were up-regulated and tumour-suppression genes were down-regulated, whereas pluripotency-related genes were up-regulated and differentiation-related genes were down-regulated, and that Wnt and Notch signalling pathways were activated during progression from ES cells to EC cells.


CONCLUSIONS
Tumourigenic characteristics of ECCs may provide a valuable insight into possible tumour progression of HESCs.
National Engineering Research Center of Human Stem Cells, Key Laboratory of Reproduction and Stem Cell, Ministry of Health, Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China.
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S
Yang
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Lin
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L
Deng
G-X
GX
Lu
D017209:Apoptosis; D018236:Carcinoma, Embryonal / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D053595:Embryonic Stem Cells / Q000166:cytology*; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor; D006801:Humans; D008954:Models, Biological; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction