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 |
|---|---|
| Pages (from-to) | 1303-1314 |
| Number of pages | 12 |
| Journal | Stem Cells |
| Volume | 28 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 01-08-2010 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Developmental Biology
- Cell Biology
Cite this
}
Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells. / Watanabe, Kazuhide; Meyer, Matthew J.; Strizzi, Luigi; Lee, Joseph M.; Gonzales, Monica; Bianco, Caterina; Nagaoka, Tadahiro; Farid, Shahram S.; Margaryan, Naira; Hendrix, Mary J.C.; Vonderhaar, Barbara K.; Salomon, David S.
In: Stem Cells, Vol. 28, No. 8, 01.08.2010, p. 1303-1314.Research output: Contribution to journal › Article
TY - JOUR
T1 - Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells
AU - Watanabe, Kazuhide
AU - Meyer, Matthew J.
AU - Strizzi, Luigi
AU - Lee, Joseph M.
AU - Gonzales, Monica
AU - Bianco, Caterina
AU - Nagaoka, Tadahiro
AU - Farid, Shahram S.
AU - Margaryan, Naira
AU - Hendrix, Mary J.C.
AU - Vonderhaar, Barbara K.
AU - Salomon, David S.
PY - 2010/8/1
Y1 - 2010/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77955797121&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955797121&partnerID=8YFLogxK
U2 - 10.1002/stem.463
DO - 10.1002/stem.463
M3 - Article
C2 - 20549704
AN - SCOPUS:77955797121
VL - 28
SP - 1303
EP - 1314
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 8
ER -