College of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK.
Institute of Metabolism and Systems Research, The University of Birmingham, Birmingham B15 2TT, UK.
Biomolecules. 2023 Aug 9;13(8):1231. doi: 10.3390/biom13081231.
Whilst S100P has been shown to be a marker for carcinogenesis, we have shown, in non-physio-pathological states, that its expression promotes trophoblast motility and invasion but the mechanisms explaining these cellular processes are unknown. Here we identify the presence of S100P in the plasma membrane/cell surface of all trophoblast cells tested, whether lines, primary extravillous (EVT) cells, or section tissue samples using either biochemical purification of plasma membrane material, cell surface protein isolation through biotinylation, or microscopy analysis. Using extracellular loss of function studies, through addition of a specific S100P antibody, our work shows that inhibiting the cell surface/membrane-bound or extracellular S100P pools significantly reduces, but importantly only in part, both cell motility and cellular invasion in different trophoblastic cell lines, as well as primary EVTs. Interestingly, this loss in cellular motility/invasion did not result in changes to the overall actin organisation and focal adhesion complexes. These findings shed new light on at least two newly characterized pathways by which S100P promotes trophoblast cellular motility and invasion. One where cellular S100P levels involve the remodelling of focal adhesions whilst another, an extracellular pathway, appears to be focal adhesion independent. Both pathways could lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation.
虽然 S100P 已被证明是癌变的标志物，但我们在非生理病理状态下表明，其表达促进滋养细胞的迁移和侵袭，但解释这些细胞过程的机制尚不清楚。在这里，我们使用生化方法纯化质膜材料、通过生物素化分离细胞表面蛋白，或通过显微镜分析，在所有经过测试的滋养细胞（无论是细胞系、原代绒毛外滋养细胞 (EVT) 细胞还是组织切片样本）中都发现了 S100P 存在于质膜/细胞膜表面。通过添加特异性 S100P 抗体进行细胞外功能丧失研究，我们的工作表明，抑制细胞表面/膜结合或细胞外 S100P 池显著减少，但重要的是只是部分减少，不同滋养细胞系以及原代 EVT 的细胞迁移和细胞侵袭。有趣的是，这种细胞迁移/侵袭的丧失不会导致整体肌动蛋白组织和粘着斑复合物发生变化。这些发现至少阐明了两种新表征的 S100P 促进滋养细胞迁移和侵袭的途径。一种途径是细胞内 S100P 水平涉及粘着斑的重塑，而另一种途径，即细胞外途径，似乎与粘着斑无关。这两种途径都可能导致新的靶点的识别，这些靶点可能解释为什么大量确认的人类妊娠因胎盘植入不良而出现并发症。
