Regulation of human trophoblast migration and invasiveness
Regulation of human trophoblast migration and invasiveness
复制标题
DOI：
10.1139/y02-016
复制
发表时间：
2002-02-01
影响因子：
2.1
通讯作者：
Lala, PK
中科院分区：
文献类型：
--
作者：
Chakraborty, C;Gleeson, LM;Lala, PK
人类胎盘是一种侵袭性结构，高度增殖、迁移和侵袭性的绒毛外滋养细胞(EVT)迁移并侵入子宫及其血管系统。利用体外培养的正常早孕EVT细胞和永生化的EVT细胞，这些细胞具有正常EVT细胞的所有表型和功能特征，研究表明，人EVT细胞的迁移/侵袭受到许多生长因子及其结合蛋白、细胞外基质(ECM)成分和一些黏附分子在妊娠期间胎儿-母体界面自分泌/旁分泌的严格调控。转化生长因子β(TGF-β)、核心蛋白聚糖(ECM中的一种蛋白多糖)和黑色素瘤细胞黏附分子(MEL-CAM)被抑制，而胰岛素样生长因子II(IGF-II)、IGF结合蛋白-1(IGFBP-1)和内皮素-1(ET-1)则刺激EVT细胞的迁移/侵袭。转化生长因子-β对EVT细胞迁移的抑制作用可能是由于整合素的上调，使细胞与细胞外基质的粘附性更强。其抗侵袭作用是通过上调基质金属蛋白酶组织抑制物-1(TIMP-1)和纤溶酶原激活物抑制物(PAI-1)，下调尿激酶型纤溶酶原激活物(UPA)而实现的。核心蛋白聚糖和MEL-CAM抑制EVT细胞迁移/侵袭的分子机制尚不清楚。IGF-II的作用是由I型I型受体(IGF-RII)独立于I型I型受体(IGF-RI)和IGFBPs介导的。IGF-II的这种作用似乎涉及抑制性G蛋白和丝裂原活化蛋白激酶(MAPK)(细胞外信号调节蛋白激酶1和2(ERK-1和ERK-2))的磷酸化。IGFBP-1通过将其Arg-Gly-Asp(RGD)结构域与α(5)β(1)整合素结合，导致粘着斑激酶(FAK)和MAPK(ERK-1和ERK-2)的磷酸化，从而刺激EVT细胞的迁移。这些研究可能会提高我们对与异常胎盘有关的疾病的理解。子痫前期的低侵袭性和滋养细胞肿瘤的高侵袭性。
The human placenta is an invasive structure in which highly proliferative, migratory, and invasive extravillous trophoblast (EVT) cells migrate and invade the uterus and its vasculature. Using in vitro propagated normal first-trimester EVT cells and immortalized EVT cells, which share all of the phenotypic and functional characteristics of the normal EVT cells, it has been shown that migration/invasion of human EVT cells is stringently regulated by many growth factors, their binding proteins, extracellular matrix (ECM) components, and some adhesion molecules in an autocrine/paracrine manner at the fetal-maternal interface in human pregnancy. Transforming growth factor beta (TGF-beta), decorin (a proteoglycan in the ECM), and melanoma cell adhesion molecule (Mel-CAM) inhibit, and insulin-like growth factor II (IGF-II), IGF-binding protein 1 (IGFBP-1), and endothelin 1 (ET-1) stimulate EVT cell migration/invasion. Inhibition of EVT cell migration by TGF-beta has been suggested to be due to upregulation of integrins, which make the cells more adhesive to the ECM. Its antiinvasive action is due to an upregulation of tissue inhibitor of matrix metalloprotease 1 (TIMP-1) and plasminogen activator inhibitor (PAI-1) and a downregulation of urokinase-type plasminogen activator (uPA). Molecular mechanisms of inhibition of migration/invasion of EVT cells by decorin and Mel-CAM remain to be identified. IGF-II action has been shown to be mediated by IGF type I receptors (IGF-RII) independently of IGF type I receptors (IGF-RI) and IGFBPs. This action of IGF-II appears to involve inhibitory G proteins and phosphorylation of mitogen-activated protein kinase (MAPK) (extracellular signal-regulated protein kinases 1 and 2 (ERK-1 and ERK-2)). IGFBP-1 stimulation of EVT cell migration appears to occur by binding its Arg-Gly-Asp (RGD) domain to alpha(5)beta(1) integrin, leading to phosphorylation of focal adhesion kinase (FAK) and MAPK (ERK-1 and ERK-2). These studies may improve our understanding of diseases related to abnormal placentation, viz. hypoinvasiveness in preeclampsia and hyperinvasiveness in trophoblastic neoplasms.