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

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)


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 languageEnglish
Pages (from-to)1303-1314
Number of pages12
JournalStem Cells
Issue number8
Publication statusPublished - 08-2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Medicine


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