Pluripotent human teratocarcinoma stem cells cultured
in vitro provide a resource for the study of early
embryonic development in man, as well as a means for discovery of novel
factors controlling cell differentiation and commitment. We previously
reported that the human teratocarcinoma stem cell line GCT 27X-1 could be
induced to differentiate into an endodermal progenitor cell by treatment with
high doses of retinoic acid. A search for polypeptide inducers of
differentiation in this system has identified bone morphogenetic protein-2
(BMP-2) as a potent inducer of differentiation. In cell line GCT 27X-1,
treatment with BMP-2 reduces proliferation, induces morphological changes
similar to obtained following treatment with retinoic acid, and causes a
decrease in the expression of transcripts for the stem cell markers CD30 and
Oct-4. Preliminary immunochemical studies indicate that the differentiated
cells produced by BMP-2 are endodermal precursors with a pattern of marker
expression similar to that found in retinoic acid treated cells. Models of
endoderm differentiation in humans will be useful for identifying the
molecules which mediate cell interactions in development, and in achieving
directed differentiation of cells for use in transplantation.
Inhibition of Bone Morphogenetic Protein 2 Suppresses the Stemness Maintenance of Cancer Stem Cells in Hepatocellular Carcinoma via the MAPK/ERK Pathway
