Expression of p57KIP2 reduces growth and invasion, and induces syncytialization in a human placental choriocarcinoma cell line, BeWo

Introduction: Syncytiotrophoblasts are the major components of the human placenta involved in fetal maternal exchange and hormone secretion. The syncytiotrophoblasts arise from the fusion of villous cytotrophoblasts. The cell cycle suppressor p57(KIP2) is known to be an essential molecule for proper trophoblast differentiation during placental formation. Methods: We generated p57(KIP2)-expressing BeWo transfectant cells. Proliferation assay and matrigel invasion assay were used to characterize p57(KIP2)-expressing BeWo transfectant cells. To reveal the role of p57(KIP2) in syncytialization, we proceeded syncytium formation analysis and qRT-PCR for detection of the expression levels Syncytin-1, Syncytin-2 and their receptors. Results: The human choriocarcinoma cell line, BeWo has undetectable levels of p57(KIP2) expression. Expression of p57(KIP2) reduced cell proliferation rate and extracellular matrix invasion activity. p57(KIP2) expressing cells displayed multinucleated cells associated with syncytiotrophoblast differentiation. In the syncytialization event, p57(KIP2) was found to potentiate forskolin-induced upregulation of Syncytin-2 in a cAMP-independent manner. Discussion: These results indicate that the expression of p57(KIP2) may act on the proliferation/invasion inhibitory factor and enhance the expression of Syncytin-2, which are associated with syncytialization in cytotrophoblasts.