Cyclic AMP enhances the expression of an extravillous trophoblast marker,melanoma cell adhesion molecule,in choriocarcinoma cell JEG3 and human chorionic villous explant cultures

Human trophoblasts consist of two main cell lineages, villous trophoblasts (VT) and extravillous trophoblasts (EVT). To identify the molecules which are involved in EVT differentiation, we have raised a monoclonal antibody (mAb) designated CHL1, by immunizing a mouse against human chorion laeve which is composed of EVT. By immunohistochemical analysis, the CHL1 antigen was found to be expressed on the majority of EVT but not on VT in addition to its expression on endothelial and myometrial cells. A subsequent cDNA panning method revealed that the CHL1 antigen was identical to melanoma cell adhesion molecule (MCAM, Mel-CAM, S-endo 1 or MUC18/CD146), which has been previously reported as one of the EVT markers. MCAM expression on JEG3 cells, a human choriocarcinoma-derived cell line, was significantly enhanced when they were co-cultured with isolated human decidual tissue. Various cytokines and growth factors that were reportedly present in decidual tissue failed to increase MCAM expression in JEG3 cells, but decidua-induced MCAM expression in JEG3 cells was attenuated by the addition of protein kinase A inhibitor H89. In addition, cAMP, which is known to stimulate differentiation of VT, enhanced MCAM expression in JEG3 cells. Its promoting effect on MCAM expression was also observed in human chorionic villous explant cultures. These findings suggest that a cAMP-dependent intracytoplasmic signalling pathway is involved in the differentiation mechanism of human EVT.