Document Detail


Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro.
MedLine Citation:
PMID:  2153559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
During placental development cytotrophoblast stem cells fuse to form the syncytiotrophoblast, a multinucleate cytoplasm with a brush border in contact with the maternal blood. Biochemical differentiation including the expression of placental-specific proteins and hormones accompanies this maturation. However, the biochemical mechanisms responsible for these events are unknown. We have defined a system in which single cytotrophoblast-like cells of the human choriocarcinoma (BeWo) cell line undergo fusion and extensive morphological differentiation following their treatment with effectors of cyclic AMP metabolism. Forskolin incubation caused a dose-dependent increase in intracellular and secreted cyclic AMP and a coordinate fusion of cells which yielded syncytia containing hundreds of nuclei per cytoplasm and a mature dense "placental-like" brush border. These fused cells also synthesized and secreted large amounts of both subunits of chorionic gonadotropin. However, they continued to synthesize several other placenta-specific proteins--placental-like alkaline phosphatase, placental lactogen, and SP1--at rates similar to those in control cells. Other reported effectors of cyclic AMP metabolism also induced cell fusion, although theophylline, an inhibitor of phosphodiesterase, induced fusion by a cyclic AMP-independent mechanism. Additionally, unlike the case with forskolin, treatment of BeWo cells with theophylline did not induce other morphological features of mature syncytiotrophoblasts. Thus, this system will allow one to examine the biochemical mechanism of placental cell fusion in the absence of other variables of cell differentiation.
Authors:
B Wice; D Menton; H Geuze; A L Schwartz
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  186     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  1990 Feb 
Date Detail:
Created Date:  1990-03-09     Completed Date:  1990-03-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  306-16     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Washington University School of Medicine, St. Louis, Missouri 63110.
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MeSH Terms
Descriptor/Qualifier:
Alkaline Phosphatase / biosynthesis
Cell Differentiation
Cell Fusion / drug effects
Cell Nucleus / ultrastructure
Choriocarcinoma
Chorionic Gonadotropin / metabolism
Cyclic AMP / metabolism*
Female
Forskolin / pharmacology
Humans
Microscopy, Electron
Placenta / enzymology
Placental Lactogen / biosynthesis
Pregnancy
Pregnancy-Specific beta 1-Glycoproteins / biosynthesis
Theophylline / pharmacology
Trophoblasts / drug effects,  physiology*,  ultrastructure
Tumor Cells, Cultured
Uterine Neoplasms
Chemical
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Pregnancy-Specific beta 1-Glycoproteins; 58-55-9/Theophylline; 60-92-4/Cyclic AMP; 66428-89-5/Forskolin; 9035-54-5/Placental Lactogen; EC 3.1.3.1/Alkaline Phosphatase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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