Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models
Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models
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DOI：
10.1007/s00418-002-0403-5
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发表时间：
2002-05-01
影响因子：
2.3
通讯作者：
Desoye, G
中科院分区：
文献类型：
--
作者：
Mandl, M;Haas, J;Desoye, G
绒毛外细胞滋养层细胞是胎盘的特化上皮细胞，可增殖或侵袭母体蜕膜。人们对这些过程的调控机制知之甚少。本文研究了不同剂量的胰岛素和胰岛素样生长因子-1(IGF-1)单独或与血清协同作用对人绒毛膜促性腺激素-β(hCG-β)分泌(RIA)、细胞增殖(细胞计数、细胞周期蛋白B-1水平)和侵袭[Matrigel侵袭实验、分泌基质金属蛋白酶(MMP2和9)]的影响。绒毛膜癌细胞系BeWo、JAR和JEG-3是人早孕滋养层细胞的模型。这两种生长因子都改变了hCG-β的分泌和依赖于细胞系的增殖。胰岛素对JAR细胞和JEG-3细胞的增殖有促进作用，无血清培养时对BeWo无影响。尽管在一定条件下改变了培养上清液中proMMP2的水平，但侵袭力并未受到影响。与血清有较强的协同作用。在血清存在的情况下，这两种生长因子以相似的方式抑制增殖和侵袭。由于细胞模型的分化程度不同，数据表明胰岛素和IGF-I的作用强烈依赖于血清和分化程度。推测在胰岛素缺乏条件下，IGF-I可以承担胰岛素调节滋养层功能的任务。
Extravillous cytotrophoblasts are specialised epithelial cells of the placenta that proliferate or invade the maternal decidua. Little is known about the mechanisms that regulate these processes. Here the effects of several insulin and insulin-like growth factor-I (IGF-1) doses, either singly or in synergy with serum, on human chorionic gonadotropin-beta (hCG-beta) secretion (RIA), proliferation (cell counting, cyclin B-1 levels) and invasion [Matrigel invasion assay, secretion of matrix metalloproteinases (MMP) 2 and 9] were investigated. The choriocarcinoma cell lines BeWo, JAR and JEG-3 served as models for first trimester human trophoblasts. Both growth factors altered hCG-beta secretion and proliferation dependent on the cell line. Insulin stimulated proliferation in JAR cells and, to a lesser extent, in JEG-3 cells, and when cultured in serum-free medium, BeWo was not affected. Invasion was not affected although proMMP-2 levels in culture medium were altered under some conditions. A strong synergistic effect with serum was noted. In the presence of serum both growth factors reduced proliferation and invasion in a similar fashion. Since the cell models differ by their degree of differentiation, the data demonstrate that the effects of insulin and IGF-I strongly depend on serum and the degree of differentiation. It can be speculated that IGF-I can take on tasks of insulin in the regulation of trophoblast functions under conditions of insulinopenia.