Human cytotrophoblasts adopt a vascular phenotype as they differentiate - A strategy for successful endovascular invasion?
Human cytotrophoblasts adopt a vascular phenotype as they differentiate - A strategy for successful endovascular invasion?
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DOI：
10.1172/jci119387
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发表时间：
1997-05-01
影响因子：
15.9
通讯作者：
Damsky, CH
中科院分区：
文献类型：
--
作者：
Zhou, Y;Fisher, SJ;Damsky, CH
人胎盘的建立需要胚胎细胞滋养层干细胞在绒毛膜绒毛上的浸润。这些细胞滋养层聚集成细胞柱，侵入子宫内膜和脉管系统，将胎儿锚定在母亲身上，并建立流向胎盘的血流。细胞滋养层在螺旋小动脉中定植，取代母体子宫内膜，直至子宫肌层的前三分之一。我们在这里表明，分化的细胞滋养层细胞转化其粘附受体表型，以类似于他们所取代的内皮细胞。细胞柱中的细胞滋养层细胞显示E-钙粘蛋白染色减少，并表达VE-（内皮）钙粘蛋白、血小板-内皮粘附分子-1、血管内皮粘附分子-1和α 4-整联蛋白。子宫内膜和母体血管系统中的细胞滋养层继续表达这些受体，并且与血管生成期间的内皮细胞一样，也对α V β 3染色。在功能研究中，α V β 3和VE-钙粘蛋白增强，而E-钙粘蛋白抑制，细胞滋养层侵袭。表达α 4整合素的细胞滋养层细胞在体外结合固定的VCAM-1，表明这种受体对可以介导细胞滋养层-内皮细胞或细胞滋养层-细胞滋养层相互作用在体内，在血管内入侵。在妊娠障碍先兆子痫中，其中血管内侵入保持浅表，细胞滋养层不能表达大多数这些内皮标志物（Zhou等人，1997. J. Clin. Invest. 99：2152-2164.），提示这种粘附表型转换是成功的血管内侵入和正常胎盘形成所必需的。
Establishment of the human placenta requires that fetal cytotrophoblast stem cells in anchoring chorionic villi become invasive. These cytotrophoblasts aggregate into cell columns and invade both the uterine interstitium and vasculature, anchoring the fetus to the mother and establishing blood flow to the placenta. Cytotrophoblasts colonizing spiral arterioles replace maternal endothelium as far as the first third of the myometrium. We show here that differentiating cytotrophoblasts transform their adhesion receptor phenotype so as to resemble the endothelial cells they replace. Cytotrophoblasts in cell columns show reduced E-cadherin staining and express VE-(endothelial) cadherin, platelet-endothelial adhesion molecule-1, vascular endothelial adhesion molecule-1, and alpha 4-integrins. Cytotrophoblasts in the uterine interstitium and maternal vasculature continue to express these receptors, and, like endothelial cells during angiogenesis, also stain for alpha V beta 3. In functional studies, alpha V beta 3 and VE-cadherin enhance, while E-cadherin restrains, cytotrophoblast invasiveness. Cytotrophoblasts ex-pressing alpha 4 integrins bound immobilized VCAM-1 in vitro, suggesting that this receptor-pair could mediate cytotrophoblast-endothelium or cytotrophoblast-cytotrophoblast interactions in vivo, during endovascular invasion. In the pregnancy disorder preeclampsia, in which endovascular invasion remains superficial, cytotrophoblasts fail to express most of these endothelial markers (Zhou et al., 1997. J. Clin. Invest. 99:2152-2164.), suggesting that this adhesion phenotype switch is required for successful endovascular invasion and normal placentation.