THE EFFECT OF HEXAPEPTIDES ON ATTACHMENT AND OUTGROWTH OF MOUSE BLASTOCYSTS CULTURED INVITRO - EVIDENCE FOR THE INVOLVEMENT OF THE CELL RECOGNITION TRIPEPTIDE ARG-GLY-ASP
THE EFFECT OF HEXAPEPTIDES ON ATTACHMENT AND OUTGROWTH OF MOUSE BLASTOCYSTS CULTURED INVITRO - EVIDENCE FOR THE INVOLVEMENT OF THE CELL RECOGNITION TRIPEPTIDE ARG-GLY-ASP
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DOI：
10.1073/pnas.83.18.6751
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发表时间：
1986-09-01
影响因子：
11.1
通讯作者：
LENNARZ, WJ
中科院分区：
文献类型：
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作者：
ARMANT, DR;KAPLAN, HA;LENNARZ, WJ
哺乳动物胚胎的非贴壁滋养外胚层细胞分化为具有贴壁能力的滋养层细胞似乎是侵入子宫间质的先决条件。为了研究不受母体环境限制的滋养层分化的分子基础，我们使用了一个模型系统，其中滋养层细胞在体外发生附着和生长。最近，人们发现，无论是纤连蛋白或层粘连蛋白，这两者都是细胞外基质的糖蛋白的子宫基质，将支持滋养层在体外生长。在这项研究中，我们报告说，在纤连蛋白包被的培养皿上的囊胚的生长受到抑制，在剂量依赖性的方式由含有序列Arg-Gly-Asp的六肽的存在下，这已被证明是由纤连蛋白受体识别。这种肽对层粘连蛋白介导的滋养层细胞生长没有影响，表明滋养层细胞含有不同的纤维连接蛋白和层粘连蛋白的细胞表面受体。滋养层附着和有限的生长也可以在与六肽Gly-Arg-Gly-Asp-Ser-Pro偶联的培养皿上获得。然而，在这些条件下，滋养层细胞的向外迁移似乎减少。玻连蛋白，另一种粘附分子，显然是通过识别Arg-Gly-Asp序列的细胞表面受体与细胞结合，也能够支持滋养层生长。这些研究结果表明，滋养外胚层细胞分化成具有侵袭性表型的滋养层细胞可能涉及纤连蛋白和可能含有Arg-Gly-Asp识别序列的其他蛋白质的细胞表面受体的产生。
Differentiation of the nonadherent trophectoderm cells of the mammalian embryo into attachment competent trophoblast cells appears to be a prerequisite to invasion of the uterine stroma. To investigate the molecular basis of trophoblast differentiation free of maternal environmental constraints, we used a model system in which attachment and outgrowth of trophoblast cells occurs in vitro. Recently, it was found that either fibronectin or laminin, both of which are extracellular matrix glycoproteins of the uterine stroma, will support trophoblast outgrowth in vitro. In this study we report that the outgrowth of blastocysts on fibronectin-coated dishes is inhibited in a dose-dependent manner by the presence of a hexapeptide containing the sequence Arg-Gly-Asp, which has been shown previously to be recognized by the fibronectin receptor. This peptide had no effect on lamin-mediated trophoblast outgrowth, suggesting that the trophoblasts contain different cell surface receptors for fibronectin and laminin. Trophoblast attachment and limited outgrowth also could be obtained on dishes to which the hexapeptide Gly-Arg-Gly-Asp-Ser-Pro was coupled. Under these conditions, however, outward migration of the trophoblast cells appeared to be reduced. Vitronectin, another adhesion molecule that apparently binds to cells via a cell surface receptor that recognizes Arg-Gly-Asp sequences, also was capable of supporting trophoblast outgrowth. These findings suggest that differentiation of cells of the trophectoderm into trophoblast cells with an invasive phenotype may involve the production of cell surface receptors for fibronectin and possibly for other proteins that contain the Arg-Gly-Asp recognition sequence.