Janneau Jean-Louis, Maldonado-Estrada Juan, Tachdjian Gérard, Miran Isabelle, Motté Nelly, Saulnier Patrick, Sabourin Jean-Christophe, Coté Jean-François, Simon Bénédicte, Frydman René, Chaouat Gérard, Bellet Dominique
Laboratoire d'Immunologie des Tumeurs ESA 8067 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques de Paris, Université René Descartes-Paris 5, Paris.
J Clin Endocrinol Metab. 2002 Nov;87(11):5336-9. doi: 10.1210/jc.2002-021093.
Once initiated, invasion of trophoblast cells must be tightly regulated, particularly in early pregnancy. The mechanisms necessary for the invasion and migration of trophoblast cells are thought to be related to those involved in the invasive and metastatic properties of cancer cells. Quantitative PCR was used to measure, in trophoblast cells, the transcriptional expression profiles of four genes, INSL4, BRMS1, KiSS-1 and KiSS-1R, reported to be implicated in tumor invasion and metastasis. Laser capture microdissection and purification of trophoblast cells demonstrate that, as already known for INSL4, BRMS1, KiSS-1 and KiSS-1R are expressed by the trophoblast subset of placental tissues. Expression profiles of these genes studied in early placentas (7-9 weeks, n=55) and term placentas (n=11) showed that expression levels of BRMS1 are higher in term than in early placentas, while expression levels of KiSS-1R are higher in early than in term placentas. Low levels of expression of BRMS1 were observed in normal pregnancies, in molar pregnancies and in choriocarcinoma cell lines BeWo, JAR and JEG3 while, in striking contrast, the expression levels of INSL4, KiSS-1 and Kiss-1R were increased in both early placentas and molar pregnancies and were reduced in choriocarcinoma cells. These transcriptional expression profiles are in favor of a predominant role of INSL4, KiSS-1 and KiSS-1R in the control of the invasive and migratory properties of trophoblast cells.
一旦启动,滋养层细胞的侵袭必须受到严格调控,尤其是在妊娠早期。滋养层细胞侵袭和迁移所需的机制被认为与癌细胞的侵袭和转移特性所涉及的机制有关。定量PCR用于测量滋养层细胞中四个基因INSL4、BRMS1、KiSS-1和KiSS-1R的转录表达谱,据报道这些基因与肿瘤侵袭和转移有关。激光捕获显微切割和纯化滋养层细胞表明,正如已知的INSL4一样,BRMS1、KiSS-1和KiSS-1R由胎盘组织的滋养层亚群表达。在早期胎盘(7 - 9周,n = 55)和足月胎盘(n = 11)中研究这些基因的表达谱,结果显示BRMS1的表达水平在足月胎盘中高于早期胎盘,而KiSS-1R的表达水平在早期胎盘中高于足月胎盘。在正常妊娠、葡萄胎妊娠以及绒毛膜癌细胞系BeWo、JAR和JEG3中观察到BRMS1的低表达水平,而与之形成鲜明对比的是,INSL4、KiSS-1和Kiss-1R的表达水平在早期胎盘和葡萄胎妊娠中均升高,在绒毛膜癌细胞中降低。这些转录表达谱支持INSL4、KiSS-1和KiSS-1R在控制滋养层细胞的侵袭和迁移特性中起主要作用。