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Investigation of controlled human extravillous trophoblast invasion

受控的人绒毛外滋养细胞侵袭的研究

基本信息

批准号：
11671612
负责人：
HIGUCHI Toshihiro
金额：
$ 2.3万
依托单位：
KYOTO UNIVERSITY (C)(2)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671612/
关键词：
Trophoblast monoclonal antibody implantation placentation invasion

项目摘要

Human trophoblasts differentiate into two main cell lineages : villous and extravillous cells. Villous trophoblasts cover the chorionic villi of the placenta, their function being to transport oxygen and nutrients from the mother to the fetus. In contrast, extravillous trophoblasts (EVT) invade maternal uterus and also migrate up the spiral arteries, transforming them into large vessels of low resistance. Many aspects of EVT invasion are similar to events that occur during tumor cell invasion. However, unlike tumor invasion, EVT invasion is precisely regulated, confined spatially to the uterus and temporally to early pregnancy. The mechanism of controlled EVT invasion is not clarified well.Therefore in this project, we first identified molecules which specifically express in EVT by several methods. Thereafter, we examined the role of each molecule in human trophoblasts, especially in their controlled invasiveness.We raised mouse mAb against human term chorion laeve (its contains abunda … More nt EVT) to identify novel molecules which are expressed in EVT.Several mAb clones which react with EVT were obtained, and their antigens were analyzed by amino acid sequencing, cDNA panning, or by immunoscreening method. These analyses revealed that integrin alpha 5, cytokeratin 18, and melanoma cell adhesion molecule (MCAM) are expressed in EVT.In addition, mAb 5-23 recognized the unknown cell surface protein of 200 kD.Besides mAb analyses, we carried out cDNA microarray analysis to identify genes which is differently expressed in non-invasive EVT of 3rd trimester chorion laeve compared with still invasive EVT of 1st trimester placenta. Several expressed sequence tag (EST) of unknown function were identified. Among these EST, EST9 was predominantly expressed in 1st trimester placenta which contains invasive EVT.Full length cDNA was determined by 5'RACE, and resultant EST9 mRNA of 6kb encoded a putative transcription factor of 40kD protein. Functions of EST9 in human trophoblast are now under investigation. Less

人类滋养层分化为两种主要细胞谱系：绒毛细胞和绒毛外细胞。绒毛滋养层覆盖胎盘的绒毛膜绒毛，其功能是将氧气和营养物质从母亲输送到胎儿。相比之下，绒毛外滋养层细胞（EVT）侵入母体子宫，并沿着螺旋动脉向上迁移，将其转变为低阻力的大血管。 EVT 侵袭的许多方面与肿瘤细胞侵袭过程中发生的事件相似。然而，与肿瘤侵袭不同，EVT 侵袭受到精确调控，空间上仅限于子宫，时间上仅限于妊娠早期。受控EVT侵袭的机制尚不清楚。因此，在本项目中，我们首先通过多种方法鉴定了EVT中特异性表达的分子。此后，我们检查了每个分子在人滋养层中的作用，特别是在其受控侵袭性方面。我们针对人足绒毛膜 laeve（其包含 abunda … More nt EVT）培养了小鼠 mAb，以鉴定在 EVT 中表达的新分子。获得了几个与 EVT 反应的 mAb 克隆，并通过氨基酸测序、cDNA 淘选或通过免疫筛选方法。这些分析表明，整合素α 5、细胞角蛋白18和黑色素瘤细胞粘附分子（MCAM）在EVT中表达。此外，mAb 5-23识别200 kD的未知细胞表面蛋白。除了mAb分析之外，我们还进行了cDNA微阵列分析，以鉴定在妊娠第三个月绒毛膜层的非侵入性EVT中与对照组相比有不同表达的基因。妊娠早期胎盘仍为侵入性 EVT。鉴定了几个功能未知的表达序列标签（EST）。在这些EST中，EST9主要在含有侵入性EVT的妊娠早期胎盘中表达。通过5'RACE测定全长cDNA，所得6kb的EST9 mRNA编码40kD蛋白质的推定转录因子。 EST9 在人类滋养层中的功能目前正在研究中。较少的