Cyclic AMP enhances the expression of an extravillous trophoblast marker, melanoma cell adhesion molecule, in choriocarcinoma cell JEG3 and human chorionic villous explant cultures
Cyclic AMP enhances the expression of an extravillous trophoblast marker, melanoma cell adhesion molecule, in choriocarcinoma cell JEG3 and human chorionic villous explant cultures
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DOI：
10.1093/molehr/gag044
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发表时间：
2003-06-01
影响因子：
4
通讯作者：
Fujii, S
中科院分区：
文献类型：
--
作者：
Higuchi, T;Fujiwara, H;Fujii, S
人滋养层细胞由两种主要细胞谱系组成，绒毛滋养层细胞（VT）和绒毛外滋养层细胞（EVT）。为了鉴定参与EVT分化的分子，我们通过免疫小鼠抗由EVT组成的人绒毛膜层，制备了命名为CHL 1的单克隆抗体（mAb）。通过免疫组化分析，CHL 1抗原被发现表达在大多数EVT上，但除了在内皮细胞和子宫肌层细胞上表达之外，在VT上不表达。随后的cDNA淘选方法显示，CHL 1抗原是相同的黑色素瘤细胞粘附分子（MCAM，Mel-CAM，S-endo 1或MUC 18/CD 146），这是以前报道的EVT标志物之一。人绒毛膜癌衍生细胞系JEG 3细胞上的MCAM表达在与分离的人蜕膜组织共培养时显著增强。据报道，蜕膜组织中存在的各种细胞因子和生长因子未能增加JEG 3细胞中MCAM的表达，但通过加入蛋白激酶A抑制剂H89，可以减弱JEG 3细胞中蜕膜诱导的MCAM表达。此外，已知刺激VT分化的cAMP增强JEG 3细胞中的MCAM表达。在人绒毛组织培养中也观察到其对MCAM表达的促进作用。这些结果表明，cAMP依赖的胞质内信号通路参与了人EVT的分化机制。
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.