Expression of tissue factor and TF-mediated integrin regulation in HTR-8/SVneo trophoblast cells

Placenta is a crucial source of Tissue Factor (TF) to initiate coagulation. As far as the TF is concern, aberrant expression of TF has been reported to have a significant role in thrombosis, inflammation, cancer metastasis and atherosclerosis. It is evident that TF and TF-FVIIa complex has major roles in the disease process beyond hemostasis and thrombosis. On the other hand, TF-FVII-dependent signaling primarily activates PAR2 and inducing pro-angiogenic and immune-modulating cytokines in tumor environment. However, the role of TF has not been delineated in placental functions. Integrin typically binds to the extracellular matrix which in turn mediate cell-cell adhesion and cell behavior for migration. Dysregulation of integrin expression affects cell interaction, proliferation, and migration. Therefore, this study aims to ascertain the expression of TF in HTR-8/SVneo trophoblast cell line and its role in signal transduction of integrin (ITGα1, ITGα2, ITGβ1) regulation concerning the invasion of trophoblasts. We have used RT-PCR and Western blot for the gene and protein expression analysis respectively. In addition, cell migration assays, MTT, and DAPI were performed to examine migration, cytotoxicity and apoptosis effect of FVIIa. The results suggest that the gene and protein level expressions of TF were predominant in HTR-8/SVneo cell line. Further, the cytotoxicity and apoptosis in HTR-8/SVneo cells were not observed when treated with FVIIa. The cells treated with FVIIa shown a dose-dependent up-regulation of integrin(s) (**p < 0.01, *p < 0.05) when compared to control. Migration of the HTR-8/SVneo cells was observed without any apoptosis in FVIIa-treated cells when compared to that of control. On the whole, these observations delineated the TF-FVIIa interaction in modulating the TF-dependent integrin signal transduction in HTR-8/SVneo trophoblast cell line.