Cripto-1 is a Cell Surface Marker for a Tumorigenic, Undifferentiated Subpopulation in Human Embryonal Carcinoma Cells

Overview

Journal Stem Cells

Publisher Oxford University Press

Specialties Cell Biology
Reproductive Medicine

Date 2010 Jun 16

PMID 20549704

Citations 36

Authors

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

Affiliations

Soon will be listed here.

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-1(High) and a CR-1(Low) population. By segregating CR-1(High) and CR-1(Low) populations of NTERA2/D1 EC cells by fluorescence-activated cell sorting, we demonstrated that CR-1(High) cells were more tumorigenic than CR-1(Low) cells by an in vitro tumor sphere assay and by in vivo xenograft formation. The CR-1(High) 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.

Citing Articles

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Expression and prognostic value of Cripto-1 in early non-small cell lung cancer.

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Understanding the role of Cripto-1 in cancer progression and therapeutic strategies.

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CRIPTO-1 Is Immunolocalized in the Syncytiotrophoblast of Ampullary Pregnancies.

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