Signal transduction in trophoblast invasion
Signal transduction in trophoblast invasion
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DOI：
10.1159/000087834
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Markert, UR
中科院分区：
文献类型：
--
作者：
Fitzgerald, JS;Busch, S;Markert, UR
在怀孕的前三个月，胎盘中分化良好的初级细胞，即滋养层细胞，以一种类似于恶性肿瘤的侵袭性和破坏性的方式生长，但在空间和时间上受到限制。滋养层细胞与其恶性对应的人绒毛癌细胞的比较，为理解恶性生长的起源或发展提供了一个有吸引力的模型。已知多种细胞因子和生长因子影响滋养层细胞的迁移(如EGF、IGF-2、HGF)、增殖(如瘦素、HGF、GM-CSF)和/或侵袭(如白血病抑制因子，LIF)，每个因子至少利用滋养层细胞内信号传递的一条途径。两条相互交叉的通路经常介导这些因子的信号，同时在肿瘤侵袭方面也得到了很好的证实：Janus激酶信号转导和转录激活因子(JAK-STAT)和受体相关的酪氨酸激酶-丝裂原活化蛋白激酶(RTK-MAPK)通路。正如一系列基因敲除实验证明的那样，这两条途径总体上对生殖是有害的，部分也是对胎盘发育有害的。每个途径的某些方面也参与了滋养层细胞的侵袭，例如STAT3在侵袭性早孕滋养层细胞中被结构性激活，而ERK在中间滋养层细胞中可被检测到，这是一种侵袭性表型。在几个细胞系统中已经描述了在这些通路之间的几个交叉点的相互作用，因此在滋养层细胞中似乎也是如此。在这篇综述中，提到了一些可能的相互作用领域。
During the first trimester of pregnancy, well-differentiated primary cells of the placenta known as trophoblast cells grow in an invasive and destructive fashion similar to malignancies, but limited in space and time. The comparison of trophoblast cells with their malignant counterpart, human choriocarcinoma cells, offers an attractive model to understand the origin or development of malignant growth. Several cytokines and growth factors are known to influence trophoblast migration (eg EGF, IGF-2, HGF), proliferation (eg leptin, HGF, GM-CSF) and/or invasion (eg leukemia inhibitory factor, LIF), each factor utilizing at least one pathway for intracellular signaling in the trophoblast. Two pathways that are crossed especially often mediate the signals of these factors and are simultaneously well established in terms of tumor invasion: the Janus kinase-signal transducers and activators of transcription (Jak-Stat) and receptor-associated tyrosine kinase-mitogen-activated protein kinase (RTK-MAPK) pathways. These two pathways are detrimental for reproduction in general, and in part for placenta development, as a series of knockout experiments demonstrate. Aspects of each pathway are also implicated to be involved in trophoblast invasion, eg STAT3 is constitutively activated in invasive first trimester trophoblast cells, and activated ERK is detectable in intermediate trophoblast cells, an invasive phenotype. Interaction at several intersection points between the pathways has been described in several cell systems so that the same would seem to be possible in trophoblast cells. In this review, some of the possible areas of interaction are alluded to.