Extracellular matrix composition and hypoxia regulate the expression of HLA-G and integrins in a human trophoblast cell line
Extracellular matrix composition and hypoxia regulate the expression of HLA-G and integrins in a human trophoblast cell line
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DOI：
10.1095/biolreprod62.3.739
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发表时间：
2000-03-01
影响因子：
3.6
通讯作者：
Armant, DR
中科院分区：
文献类型：
--
作者：
Kilburn, BA;Wang, J;Armant, DR
在人胎盘过程中，卵泡外细胞滋养细胞从绒毛膜绒毛中出现，与蜕膜接触并侵入子宫壁。当从妊娠早期胎盘中分离出来时，细胞滋养层细胞在体外进行分步分化，再现了体内观察到的表型异质性。我们检测了一个细胞系HTR-8/SVneo，该细胞系是从人类妊娠早期的细胞滋养细胞中建立的，以确定这些细胞是否具有之前描述的一些独特的细胞滋养细胞特征。在无血清低氧条件下（2%氧浓度）培养时，HTR-8/SVneo细胞增殖增加，三维基底膜（基质）侵袭减少。在包被单个细胞外基质蛋白的表面培养时，HTR-8/SVneo细胞表达细胞角蛋白，但不表达滋养层特异性的主要组织相容性蛋白HLA-G。然而，HTR-8/SVneo细胞接触Matrigel后，HLA-G表达被诱导，α 5整合素亚基的表达相对不受基质组成的影响，而将细胞转移到Matrigel后，α 1上调，α 6下调。缺氧增加了Matrigel上α 6的表达，降低了α 1和HLA-G的表达，HTR-8/SVneo细胞保留了与妊娠早期人类细胞滋养层细胞原代培养相关的几个重要特征，包括它们对变化的母体环境的行为改变。
During human placentation, extravillous cytotrophoblast cells emerge from chorionic villi contacting the decidua to invade the uterine wall. When isolated from first-trimester placentae, cytotrophoblast cells undergo step-wise differentiation in vitro that recapitulates the phenotypic heterogeneity observed in vivo. We examined a cell line, HTR-8/SVneo, that has been established from human first-trimester cytotrophoblast to determine whether these cells possess some of the unique cytotrophoblast characteristics that have been described previously. Exposure during serum-free culture to hypoxic conditions (2% oxygen concentration) increased HTR-8/SVneo cell proliferation and reduced invasion of a three-dimensional basement membrane (Matrigel), During culture on surfaces coated with individual extracellular matrix proteins, HTR-8/SVneo cells expressed cytokeratin but not the trophoblast-specific major histocompatibility protein, HLA-G. However, HLA-G expression was induced in HTR-8/SVneo cells that contacted Matrigel, Expression of the alpha 5 integrin subunit was relatively unaffected by matrix composition, whereas alpha 1 was up-regulated and alpha 6 was down-regulated after transferring cells to Matrigel. Hypoxia increased alpha 6 and decreased both alpha 1 and HLA-G expression on Matrigel, HTR-8/SVneo cells retain several important characteristics associated with primary cultures of first-trimester human cytotrophoblast cells, including their altered behavior in response to a changing maternal environment.