基质金属蛋白酶MMP-26能有效促进人绒毛膜上皮癌细胞JEG-3浸润能力

胚胎植入过程中,滋养层细胞浸润与肿瘤的迁移过程非常相似,但显著的区别在于前者是受严格调控的有节制的浸润,基质金属蛋白酶(MMPs)的许多成员在其中起重要的作用.MMP-26是近年来发现的MMPs家族的新成员,它在滋养层细胞中的作用所知甚少.利用国际常用的人滋养层细胞模型——人绒毛膜上皮癌细胞系(JEG-3)作为体外实验模型,探讨MMP-26在人滋养层细胞浸润调节中的作用.将含有MMP-26全长cDNA的pCR3.1质粒转染到JEG-3细胞中,获得过量表达MMP-26基因的稳定细胞系JEG-3/MMP-26;细胞浸润分析表明JEG/MMP-26细胞的浸润能力较母本细胞明显增强;RT-PCR和明胶酶谱分析显示JEG-3/MMP-26细胞中MMP-9的表达和分泌水平提高;双荧光免疫细胞化学进一步显示MMP-26和MMP-9蛋白在细胞中有共定位现象.上述结果表明MMP-26能有效促进人滋养层细胞浸润,其作用可能是通过与其他MMP分子(如MMP-9)的协调来实现的.

Effect of Matrix Metalloproteinase-26 on Cell Invasiveness in Human Choriocarcinomal Cell Line JEG-3

Trophoblast invasion during implantation mimics the process of tumor metastasis in some aspects, however with a significant difference in that the former is strictly controlled. Several members of matrix metalloproteinases (MMPs) family have been shown to play crucial roles in regulating trophoblast cell invasion. MMP-26 is a newly identified MMP family member, and its functions in human trophoblast cells have yet to be elucidated. A well-accepted human trophoblast cell model--choriocarcinoma cell line (JEG-3) was used as in vitro model to investigate the involvement of MMP-26 in trophoblast cell invasion. Expressing pCR3.1 plasmid containing MMP-26 cDNA was transfected into JEG-3 cells, and a stable cell line with over-expressed MMP-26 was named as JEG-3/MMP-26. Transwell insert invasion assay showed that cell invasiveness in JEG-3/MMP-26 cells was significantly promoted. Data of RT-PCR and gelatin zymography demonstrated that the mRNA expression and zymogen secretion of MMP-9 were increased in these cells. Double immunofluorescent staining revealed co-localization of MMP-26 and MMP-9 proteins in JEG-3/MMP-26 cells. The data indicated that MMP-26 was involved in invasion-promoting regulation of human trophoblast cells, and it may function, at least in part, through coordination with other MMPs such as MMP-9.