INSERM U972 Les Cellules Souches: de leurs niches aux applications thérapeutiques, Hôpital P. Brousse, Bâtiment Lavoisier, 14 avenue P.V. Couturier, 94800 Villejuif, France.
Virchows Arch. 2013 Jun;462(6):653-63. doi: 10.1007/s00428-013-1427-z. Epub 2013 May 17.
Trophoblast cell adhesion and migration are carefully coordinated during normal placental development. We have compared the expression of three adhesion molecules, E-cadherin, β-catenin, and Lewis x, by immunohistochemistry during normal trophoblast differentiation, and in hydatidiform moles and choriocarcinomas. Both E-cadherin and β-catenin were expressed in normal placenta cytotrophoblast, and this expression decreased with trophoblast maturation. E-cadherin was mainly localized along the contact between cytotrophoblast and syncytiotrophoblast, which indicates its role in the differentiation of the syncytial layer. Lewis x disappeared progressively during differentiation of normal villous vessels, and was expressed in molar pregnancies. Interestingly, whereas choriocarcinomas were not, or poorly, stained, invasive hydatidiform moles (invHMs) strongly expressed Lewis x in vascular structures. This observation correlated well with E-cadherin and β-catenin expression and suggests that these three markers are associated with the invasive transformation. The presence of robust endothelial structures in invHMs could also explain their ability to maintain organized villous architecture (contrary to metastatic choriocarcinomas) during their invasion of extrauterine tissues such as the lung or the brain after dissemination through the blood flow. In our hands, Lewis x appeared to be a new, reliable marker that can be used to clearly distinguish invHMs from choriocarcinomas.
滋养细胞的黏附和迁移在正常胎盘发育中是被精细协调的。我们通过免疫组化比较了三种黏附分子 E-钙黏蛋白、β-连环蛋白和 Lewis x 在正常滋养细胞分化、葡萄胎和绒毛膜癌中的表达。E-钙黏蛋白和β-连环蛋白均在正常胎盘细胞滋养细胞中表达,且这种表达随着滋养细胞的成熟而减少。E-钙黏蛋白主要定位于细胞滋养层与合体滋养层的接触处,这表明它在合胞层的分化中起作用。Lewis x 在正常绒毛血管的分化过程中逐渐消失,并在葡萄胎中表达。有趣的是,虽然绒毛膜癌不表达或表达不佳,但侵袭性葡萄胎(invHMs)在血管结构中强烈表达 Lewis x。这一观察结果与 E-钙黏蛋白和β-连环蛋白的表达很好地相关,表明这三种标志物与侵袭性转化有关。invHMs 中存在强健的内皮结构也可以解释它们在通过血流扩散到肺部或脑部等子宫外组织的侵袭过程中,能够维持有组织的绒毛状结构(与转移性绒毛膜癌相反)的能力。在我们的研究中,Lewis x 似乎是一个新的、可靠的标志物,可以清楚地区分 invHMs 和绒毛膜癌。