S100P enhances the motility and invasion of human trophoblast cell lines.

S100P enhances the motility and invasion of human trophoblast cell lines.
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S100P 增强人滋养层细胞系的运动性和侵袭性。

DOI:
10.1038/s41598-018-29852-2
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发表时间:
2018-07-31
期刊:
影响因子:
4.6
通讯作者:
Gross SR
Gross SR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Tabrizi MEA;Lancaster TL;Ismail TM;Georgiadou A;Ganguly A;Mistry JJ;Wang K;Rudland PS;Ahmad S;Gross SR

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S100 P已被证明是致癌作用的标志物,其中其在实体瘤中的表达与转移和不良患者预后相关。然而,这种蛋白质在任何生理过程中的作用都是未知的。在这里,我们首先表明,S100 P在滋养层细胞在体内以及在一些相应的细胞系在培养中表达。我们证明,S100 P主要是在胎盘形成的早期阶段,其最高的表达水平发生在妊娠的前三个月,特别是在入侵列和锚定绒毛。通过分别过表达或敲低S100 P表达来获得或丧失功能的研究,我们的工作表明,S100 P在不同的滋养层细胞和早期妊娠EVT细胞系中刺激细胞运动和细胞侵袭。有趣的是,细胞侵袭被认为比细胞迁移受到更显著的影响。我们的研究结果表明,S100 P可能是作为一个重要的调节滋养层细胞入侵胎盘。这一发现揭示了迄今为止尚未表征的分子机制,这可能反过来导致识别新的靶点,这可能解释为什么大量确认的人类妊娠会因胎盘植入不良而发生并发症。
S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein’s role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation.
GATA3抑制GCM1活性和滋养细胞侵袭。
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