Regulation of trophoblast beta1-integrin expression by contact with endothelial cells

When cultured alone, trophoblasts expressed low levels of β1 integrin as determined by quantitative immunofluorescence microscopy. When trophoblasts were cultured on top of endothelial cells for 24 h, the expression of trophoblast β1 integrin was significantly increased as determined by image analysis. β1 Integrin expression was not increased when trophoblasts were cultured with endothelial cell-conditioned medium, suggesting that upregulation requires direct contact between trophoblasts and endothelial cells. To identify endothelial cell surface molecules responsible for induction of trophoblast integrin expression, trophoblasts were cultured in dishes coated with recombinant platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), or αVβ3 integrin. Trophoblast β1 integrin expression (assessed by immunofluorescence microscopy and Western blotting) was increased when PECAM-1 or αVβ3 integrin, but not ICAM-1, was used as substrate.Direct contact between trophoblasts and endothelial cells increases the expression of trophoblast β1 integrin.As part of the implantation process and development of the placenta in human and non-human primates, migratory trophoblasts penetrate the uterine epithelium, invade the uterine matrix, and enter the uterine vasculature [1-7]. These invasive trophoblasts show increased expression of β1 and α1 integrins and down-regulation of β4 integrin when compared to non-invasive villous trophoblast cells [8-11]. Integrins are heterodimeric transmembrane proteins that function in cell-matrix and cell-cell adhesion. Integrins also function in cell signaling. Our previous studies suggest a role for trophoblast β1 integrin in trophoblast adhesion to endothelial cells [12]. Beta 1 integrins, and integrins in general, are also known to be involved in cell migratory activity [13-17]. The factors responsible for regulating the acquisition of the migratory trophoblast phenotype, and for controlling integrin expr