Grümmer R, Hellmann P, Traub O, Soares M J, el-Sabban M E, Winterhager E
Institute of Anatomy, University Hospital, Essen, Germany.
Exp Cell Res. 1996 Aug 25;227(1):23-32. doi: 10.1006/excr.1996.0245.
The controlled invasiveness of the trophoblast is based on the balance between invasive properties at implantation and the differentiation program of the developing placenta. During placental development in rats a switch of connexin gene expression has been observed in parallel to the switch from the invasive to the differentiated phenotype of trophoblast cells. To investigate the role of connexin expression for trophoblast invasion, proliferation, and differentiation, we studied one rat trophoblast (HRP-1) and one rat choriocarcinoma cell line (Rcho-1). The choriocarcinoma cells were characterized by expression of cx31 and a lack of E-cadherin, corresponding to the invasive trophoblast in vivo, whereas HRP-1 cells expressed cx43, normally found in the spongiotrophoblast and in late giant cells, and E-cadherin. Upon retinoic acid treatment, Rcho-1 cells irreversibly lost cx31 expression, accompanied by a loss of functional coupling. No changes in regard to connexin expression and cell-cell communication could be observed in HRP-1 cells. In addition, treatment of Rcho-1 cells with retinoic acid for 7 days upregulated expression of cx43 transcript, but no protein could be found. Proliferation was clearly reduced and the mean volume of cells doubled from Day 4 to Day 7 of retinoic acid treatment in Rcho-1 cells, while both parameters were not affected in HRP-1 cells. Both cell lines showed a similar invasion rate using a Matrigel invasion assay, and invasion was equally suppressed upon retinoic acid treatment. Thus the different connexin expression appears more likely to play a role in regulating proliferation and differentiation along the multilineage pathway than invasiveness of rat trophoblast cells.
滋养层细胞的可控侵袭性基于植入时的侵袭特性与发育中胎盘的分化程序之间的平衡。在大鼠胎盘发育过程中，观察到连接蛋白基因表达的转变与滋养层细胞从侵袭性表型向分化表型的转变同步。为了研究连接蛋白表达对滋养层细胞侵袭、增殖和分化的作用，我们研究了一种大鼠滋养层细胞系（HRP-1）和一种大鼠绒毛膜癌细胞系（Rcho-1）。绒毛膜癌细胞的特征是cx31表达且缺乏E-钙黏蛋白，这与体内侵袭性滋养层细胞相对应，而HRP-1细胞表达cx43，通常在海绵滋养层细胞和晚期巨细胞中发现，以及E-钙黏蛋白。用视黄酸处理后，Rcho-1细胞不可逆地丧失cx31表达，并伴有功能偶联的丧失。在HRP-1细胞中未观察到连接蛋白表达和细胞间通讯的变化。此外，用视黄酸处理Rcho-1细胞7天会上调cx43转录本的表达，但未发现蛋白。在Rcho-1细胞中，视黄酸处理从第4天到第7天增殖明显降低且细胞平均体积翻倍，而这两个参数在HRP-1细胞中未受影响。使用基质胶侵袭试验，两种细胞系显示出相似的侵袭率，并且视黄酸处理后侵袭均受到同等程度的抑制。因此，不同的连接蛋白表达似乎更有可能在调节沿多谱系途径的增殖和分化中发挥作用，而不是在大鼠滋养层细胞的侵袭性方面。
