Expression, distribution and function of the focal adhesion kinase (pp125FAK) during murine ectoplacental cone outgrowthin vitro

Mouse embryo implantation is a complex process that includes trophoblast cells derived from ectoplacental cone (EPC) adhesion to and migration through the extracellular matrix (ECM) of uterine endometrium and invasion into the decidua. At the time of implantation, fibronectin (FN) is abundant in the decidua and is distributed pericellularly around each individual strornal cell, and its receptor (integrin α₅β₁) expression on trophoblast populations is up-regulated. The focal adhesion kinase, a 125 ku protein tyrosine kinase (pp125^FAK), is tyrosine phosphorylated upon integrin engagement with its ECM ligand, and its tyrosine phosphorylation sites then serve as the binding sites which couple it with cellular proteins that contain Src SH2 or SH3 domains. Through these linkages, pp125^FAK may integrate multiple signals triggered by integrins. The model of EPC culturein vitro was used to study the expression, distribution and function of pp125^FAK during EPC outgrowth on FN. Results indicated that, pp125^FAK primarily expressed and distributed in cellular focal adhesions of the front edge of trophoblast outgrowth from EPC, and was localized in the peripheral region of the individual migrating trophblast cell; antibody or antisense oligodeoxynucleotide to pp125^FAk inhibited EPC attachment and outgrowth, as well as trophoblast cells spreading and migration. This experiment demonstrated that pp125^FAK as an integrin-mediated signaling molecule was involved in EPC outgrowthin vitro, and played an important role during trophoblast cells interaction with FN.