Burrows T D, King A, Smith S K, Loke Y W
Department of Pathology, University of Cambridge, UK.
Hum Reprod. 1995 Sep;10(9):2489-500. doi: 10.1093/oxfordjournals.humrep.a136329.
At the time of implantation, the extracellular matrix proteins laminin and fibronectin are abundant in the decidua and are distributed pericellularly around each individual stromal cell. First trimester human trophoblast expresses both laminin and fibronectin receptors, specifically the alpha 1 beta 1, alpha 5 beta 1, alpha 6 beta 1 and alpha 6 beta 4 integrin heterodimers. In this study we have demonstrated that in-vitro adhesion of first trimester human trophoblast to purified extracellular matrix proteins and to purified decidual stromal cell monolayers can be inhibited by monoclonal antibodies directed against appropriate integrin subunits and by synthetic peptides containing an arginine-glycine-aspartic acid sequence. Monoclonal antibodies (mAbs) to the alpha 5 and beta 1 integrin subunits and a synthetic peptide significantly inhibited adhesion to fibronectin. Binding of trophoblast to laminin was blocked with mAbs to the alpha 6 and beta 1 but not alpha 1 and beta 4 integrin subunits. Similarly, integrin-mediated adhesion to monolayers of decidual stromal cells could be blocked with mAbs to the alpha 5, alpha 6, beta 1 and beta 4 integrin subunits. Integrin-mediated signal transduction in normal and malignant trophoblast was investigated by Western blotting. A 115 kDa protein was the major tyrosine phosphorylated protein detected in trophoblast after binding to laminin or fibronectin. The profile of tyrosine phosphorylated proteins differed for malignant trophoblast.
在植入时，细胞外基质蛋白层粘连蛋白和纤连蛋白在蜕膜中含量丰富，并围绕每个单个的基质细胞呈细胞周分布。孕早期人滋养层细胞表达层粘连蛋白和纤连蛋白受体，特别是α1β1、α5β1、α6β1和α6β4整合素异二聚体。在本研究中，我们已经证明，针对适当整合素亚基的单克隆抗体和含有精氨酸 - 甘氨酸 - 天冬氨酸序列的合成肽可以抑制孕早期人滋养层细胞与纯化的细胞外基质蛋白以及纯化的蜕膜基质细胞单层的体外黏附。针对α5和β1整合素亚基的单克隆抗体（mAbs）以及一种合成肽显著抑制了与纤连蛋白的黏附。滋养层细胞与层粘连蛋白的结合被针对α6和β1但不针对α1和β4整合素亚基的单克隆抗体所阻断。同样，针对α5、α6、β1和β4整合素亚基的单克隆抗体可以阻断整合素介导的与蜕膜基质细胞单层的黏附。通过蛋白质印迹法研究了正常和恶性滋养层细胞中整合素介导的信号转导。一种115 kDa的蛋白质是滋养层细胞在与层粘连蛋白或纤连蛋白结合后检测到的主要酪氨酸磷酸化蛋白。恶性滋养层细胞的酪氨酸磷酸化蛋白谱有所不同。
