期刊
STEM CELLS
卷 28, 期 8, 页码 1303-1314出版社
WILEY-BLACKWELL
DOI: 10.1002/stem.463
关键词
Cripto-1; Embryonal carcinoma; Nanog; Oct4; Pluripotent stem cells; Tumorigenicity
资金
- NIH, National Cancer Institute, Center for Cancer Research
- NIH [CA59702, CA121205, CA75681]
- Eisenberg Research Fund
Deregulation of stem cells is associated with the generation and progression of malignant tumors. In addition, genes that are associated with early embryogenesis are frequently expressed in cancer. Cripto-1 (CR-1), a glycosylphosphatidylinositol-linked glycoprotein, is expressed during early embryogenesis and in various human carcinomas. We demonstrated that human embryonal carcinoma (EC) cells are heterogeneous for CR-1 expression and consist of two distinct subpopulations: a CR-1(High) and a CR-1(Low) population. By segregating CR-1(High) and CR-1(Low) populations of NTERA2/D1 EC cells by fluorescence-activated cell sorting, we demonstrated that CR-1(High) cells were more tumorigenic than CR-1(Low) cells by an in vitro tumor sphere assay and by in vivo xenograft formation. The CR-1(High) population was enriched in mRNA expression for the pluripotent embryonic stem (ES) cell genes Oct4, Sox2, and Nanog. CR-1 expression in NTERA2/D1 cells was regulated by a Smad2/3-dependent autocrine loop, by the ES cell-related transcription factors Oct4/Nanog, and partially by the DNA methylation status of the promoter region. These results demonstrate that CR-1 expression is enriched in an undifferentiated, tumorigenic subpopulation and is regulated by key regulators of pluripotent stem cells. STEM CELLS 2010; 28: 1303-1314
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