Cripto-1 Is a Cell Surface Marker for a Tumorigenic, Undifferentiated Subpopulation in Human Embryonal Carcinoma Cells
| Autor: | Tadahiro Nagaoka, Joseph M. Lee, Luigi Strizzi, Matthew J. Meyer, Barbara K. Vonderhaar, Kazuhide Watanabe, Shahram Farid, Naira V. Margaryan, Caterina Bianco, Monica Gonzales, Mary J.C. Hendrix, David S. Salomon |
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| Rok vydání: | 2010 |
| Předmět: |
Pluripotent Stem Cells
Homeobox protein NANOG Chromatin Immunoprecipitation Embryonal Carcinoma Stem Cells Rex1 Cellular differentiation Blotting Western Fluorescent Antibody Technique Mice Nude Biology GPI-Linked Proteins Article Cell Line Mice SOX2 Cancer stem cell Animals Humans Induced pluripotent stem cell Homeodomain Proteins Membrane Glycoproteins Epidermal Growth Factor Reverse Transcriptase Polymerase Chain Reaction Nanog Homeobox Protein Cell Biology DNA Methylation Flow Cytometry Immunohistochemistry Molecular biology Neoplasm Proteins Cell biology Intercellular Signaling Peptides and Proteins Molecular Medicine Stem cell Octamer Transcription Factor-3 Neoplasm Transplantation Developmental Biology |
| Zdroj: | Stem Cells. 28:1303-1314 |
| ISSN: | 1549-4918 1066-5099 |
| DOI: | 10.1002/stem.463 |
| Popis: | 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-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. |
| Databáze: | OpenAIRE |
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