Hochberg A, Sibley C, Pixley M, Sadovsky Y, Strauss B, Boime I
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
J Biol Chem. 1991 May 5;266(13):8517-22.
The human placenta arises from the zygote through single cell intermediates called cytotrophoblasts that in turn give rise to a syncytium. In culture, mononucleated cytotrophoblasts exhibit little, if any, cell division but are converted to multinucleated cells. Choriocarcinoma, the malignant tumor of placenta trophoblast, comprises a mixed population of dividing cellular intermediates that resemble cytotrophoblasts but are less differentiated. Because the choriocarcinoma intermediates arise from dividing cells, the tumor may contain one or more cell types in abundance not present in the population of isolated placental cells. To study placental differentiation through cell-cell interaction, choriocarcinoma cell lines were co-cultured with placenta-derived cytotrophoblasts, and placental hormone biosynthesis, as a marker of differentiation was examined. We reasoned that intermediates formed by the tumor might interact with and complement those intermediates in the placenta-derived cytotrophoblast population. Co-culturing either the JAr or JEG choriocarcinoma cell lines with cytotrophoblasts elevated the synthesis of the chorionic gonadotropin alpha and beta subunits 10-20 fold, and human placental lactogen 5-fold. The effect was specific for these trophoblast-derived cells, since comparable quantities of Chinese hamster ovary or HeLa cells did not affect the placental cytotrophoblast culture. Further experiments suggested that the source of enhanced synthesis was the cytotrophoblasts. We propose that an interaction between cytotrophoblasts and choriocarcinoma cells occurs, which results in an increased number of differentiating cytotrophoblasts. Such co-cultures may represent a model system for examining choriocarcinoma cell interaction with normal cells, a process known to occur in vivo. The data are also consistent with the hypothesis that the regulated chorionic gonadotropin production in the placenta is determined by interaction among trophoblast cells at different stages of differentiation.
人类胎盘由受精卵通过称为细胞滋养层的单细胞中间体发育而来，细胞滋养层进而形成合体滋养层。在培养过程中，单核细胞滋养层细胞几乎不发生细胞分裂（即便有也极少），但会转变为多核细胞。绒毛膜癌是胎盘滋养层的恶性肿瘤，由类似于细胞滋养层但分化程度较低的分裂细胞中间体混合群体组成。由于绒毛膜癌细胞中间体源自分裂细胞，肿瘤可能含有一种或多种在分离的胎盘细胞群体中不存在的大量细胞类型。为了通过细胞间相互作用研究胎盘分化，将绒毛膜癌细胞系与胎盘来源的细胞滋养层细胞共培养，并检测作为分化标志物的胎盘激素生物合成。我们推测肿瘤形成的中间体可能与胎盘来源的细胞滋养层群体中的中间体相互作用并相互补充。将JAr或JEG绒毛膜癌细胞系与细胞滋养层细胞共培养，可使绒毛膜促性腺激素α和β亚基的合成提高10 - 20倍，人胎盘催乳素提高5倍。这种效应对于这些滋养层来源的细胞具有特异性，因为等量的中国仓鼠卵巢细胞或HeLa细胞不会影响胎盘细胞滋养层培养。进一步的实验表明，合成增强的来源是细胞滋养层。我们提出细胞滋养层与绒毛膜癌细胞之间发生相互作用，导致分化的细胞滋养层数量增加。这种共培养可能代表了一种用于研究绒毛膜癌细胞与正常细胞相互作用的模型系统，这一过程在体内也会发生。这些数据也与以下假设一致，即胎盘中绒毛膜促性腺激素的调节产生是由不同分化阶段的滋养层细胞之间的相互作用决定的。
