Choriocarcinoma, a highly malignant tumor arising from the trophoblast, comprises a heterogenous population of cells including cytotrophoblasts, intermediate trophoblasts, and syncytiotrophoblasts. In order to investigate trophoblast differentiation, we used centrifugal elutriation to separate cells from the JAr choriocarcinoma cell line according to their size and to further show that the resultant cell populations differ in their stage of differentiation. Two % of the cell population consists of large, multinuclear cells, which display the highest level of chorionic gonadotropin (CG) mRNAs. The increase in the CGβ mRNA with cell size is a consequence of the transcriptional mechanism, since agents which induce differentiation in JAr cells, i.e., methotrexate, increase the level of CGα and CGβ transcripts, cause a shift in cell size, and result in the formation of multinuclear cells. The multinuclear cells in the JAr population arise, at least partly, from kariokinesis without cytokinesis.

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