Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells

Kazuhide Watanabe, Matthew J. Meyer, Luigi Strizzi, Joseph M. Lee, Monica Gonzales, Caterina Bianco, Tadahiro Nagaoka, Shahram S. Farid, Naira Margaryan, Mary J.C. Hendrix, Barbara K. Vonderhaar, David S. Salomon

研究成果: Article

40 引用 (Scopus)

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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.

元の言語English
ページ(範囲)1303-1314
ページ数12
ジャーナルStem Cells
28
発行部数8
DOI
出版物ステータスPublished - 01-08-2010

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Embryonal Carcinoma Stem Cells
Pluripotent Stem Cells
Embryonic Stem Cells
Embryonic Development
Population
Neoplasms
Glycosylphosphatidylinositols
DNA Methylation
Heterografts
Genetic Promoter Regions
Genes
Glycoproteins
Flow Cytometry
Transcription Factors
Stem Cells
Carcinoma
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

これを引用

Watanabe, K., Meyer, M. J., Strizzi, L., Lee, J. M., Gonzales, M., Bianco, C., ... Salomon, D. S. (2010). Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells. Stem Cells, 28(8), 1303-1314. https://doi.org/10.1002/stem.463
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. / Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells. :: Stem Cells. 2010 ; 巻 28, 番号 8. pp. 1303-1314.
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title = "Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells",
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.",
author = "Kazuhide Watanabe and Meyer, {Matthew J.} and Luigi Strizzi and Lee, {Joseph M.} and Monica Gonzales and Caterina Bianco and Tadahiro Nagaoka and Farid, {Shahram S.} and Naira Margaryan and Hendrix, {Mary J.C.} and Vonderhaar, {Barbara K.} and Salomon, {David S.}",
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Watanabe, K, Meyer, MJ, Strizzi, L, Lee, JM, Gonzales, M, Bianco, C, Nagaoka, T, Farid, SS, Margaryan, N, Hendrix, MJC, Vonderhaar, BK & Salomon, DS 2010, 'Cripto-1 is a cell surface marker for a tumorigenic, undifferentiated subpopulation in human embryonal carcinoma cells', Stem Cells, 巻. 28, 番号 8, pp. 1303-1314. https://doi.org/10.1002/stem.463

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.

:: Stem Cells, 巻 28, 番号 8, 01.08.2010, p. 1303-1314.

研究成果: 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.

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