Abstract
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-1High and a CR-1Low population. By segregating CR-1High and CR-1Low populations of NTERA2/D1 EC cells by fluorescence-activated cell sorting, we demonstrated that CR-1High cells were more tumorigenic than CR-1 Low cells by an in vitro tumor sphere assay and by in vivo xenograft formation. The CR-1High 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.
Original language | English |
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Pages (from-to) | 1303-1314 |
Number of pages | 12 |
Journal | Stem Cells |
Volume | 28 |
Issue number | 8 |
DOIs | |
Publication status | Published - 08-2010 |
Externally published | Yes |
All Science Journal Classification (ASJC) codes
- General Medicine