Integrin switching regulates normal trophoblast invasion.
Integrin switching regulates normal trophoblast invasion.
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DOI：
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发表时间：
1994-12
期刊：
影响因子：
4.6
通讯作者：
C. Damsky;C. Librach;K. Lim;M. L. Fitzgerald;M. Mcmaster;M. Janatpour;Yan Zhou;S. Logan;S. Fisher
中科院分区：
文献类型：
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作者：
C. Damsky;C. Librach;K. Lim;M. L. Fitzgerald;M. Mcmaster;M. Janatpour;Yan Zhou;S. Logan;S. Fisher
在正常发育过程中，细胞在特定的时间和地点以受调节的方式侵入细胞外基质。一个戏剧性的例子是滋养层侵入子宫壁。先前的研究表明，滋养层细胞分化为侵袭性表型伴随着时间和空间调控的整合素库转换。在人胎盘的前三个月，α 6整联蛋白仅限于细胞滋养层（CTB）干细胞，并在侵袭性CTB中下调，而α 5 β 1和α 1 β 1整联蛋白在分化和侵袭性CTB中上调。本研究的目的是确定这些变化是否对CTB侵袭性有功能性影响。使用体外侵袭模型，我们首先确定了体外侵袭的前三个月CTB的聚集体经历与原位观察到的整合素转换相同的模式，从而验证了模型的实用性。然后，我们表明，抗体干扰涉及层粘连蛋白或IV型胶原蛋白及其整合素α 1/β 1受体的相互作用抑制CTB的侵袭，而干扰纤连蛋白和α 5/β 1纤连蛋白受体之间的相互作用加速侵袭。最后，我们报告说，妊娠后期CTB，显示大大降低了侵袭能力，也无法上调α 1 β 1复合物，提供了进一步的证据表明，这种整合素是关键的CTB入侵。这种妊娠调节是转录的。这些数据表明，在原位分化过程中观察到的整合素转换对CTB侵袭具有显著的功能后果。这些数据进一步表明，分化CTB上调平衡的侵袭加速和侵袭抑制粘附机制。我们认为这有助于调节正常着床过程中CTB浸润的深度。
Cells invade extracellular matrices in a regulated manner at specific times and places during normal development. A dramatic example is trophoblast invasion of the uterine wall. Previous studies have shown that differentiation of trophoblasts to an invasive phenotype is accompanied by temporally and spatially regulated switching of their integrin repertoire. In the first trimester human placenta, alpha 6 integrins are restricted to cytotrophoblast (CTB) stem cells and downregulated in invasive CTBs, whereas alpha 5 beta 1 and alpha 1 beta 1 integrins are upregulated in differentiating and invasive CTBs. The goal of the present study was to determine whether these changes have functional consequences for CTB invasiveness. Using an in vitro invasion model, we determined first that aggregates of invading first trimester CTBs in vitro undergo the same pattern of integrin switching as was observed in situ, thereby validating the utility of the model. We then showed that antibody perturbation of interactions involving laminin or collagen type IV and their integrin alpha 1/beta 1 receptor inhibited invasion by CTBs, whereas perturbing interactions between fibronectin and the alpha 5/beta 1 fibronectin receptor accelerated invasion. Finally, we report that later gestation CTBs, which display greatly decreased invasive capacity, are also unable to upregulate alpha 1 beta 1 complexes, providing further evidence that this integrin is critical for CTB invasion. This gestational regulation is transcriptional. These data indicate that integrin switching observed during differentiation in situ has significant functional consequences for CTB invasion. The data suggest further that differentiating CTBs upregulate counterbalancing invasion-accelerating and invasion-restraining adhesion mechanisms. We propose that this contributes to regulating the depth of CTB invasion during normal implantation.