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- Title
Cripto-1 Is a Cell Surface Marker for a Tumorigenic, Undifferentiated Subpopulation in Human Embryonal Carcinoma Cells.
- Authors
Watanabe, Kazuhide; Meyer, Matthew J.; Strizzi, Luigi; Lee, Joseph M.; Gonzales, Monica; Bianco, Caterina; Nacaoka, Tadahiro; Farid, Shahram S.; Marcaryan, Naira; Hendrix, Mary J . C .; Vonderhaar, Barbara K.; Salomon, David S.
- 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-l (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 CR1Low populations of NTERA2/D1 EC cells by fluorescence-activated cell sorting, we demonstrated that CR-1High cells were more tumorigenic than CR-1Low 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.
- Subjects
CANCER cells; EMBRYONIC stem cells; CANCER genetics; HUMAN embryology; FLUORIMETRY; XENOGRAFTS
- Publication
Stem Cells, 2010, Vol 28, Issue 8, p1303
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1002/stem.463