Saga Ævarsdóttir, Guðrún Valdimarsdóttir and Þóra Steingrímsdóttir
Pre-eclampsia is a life-threatening condition for both mother and fetus, occurring in 2-10% of all pregnancies. During normal placental development, trophoblasts invade the maternal spiral artery and replace the endothelial cells. This change causes reduced artery resistance enabling more blood flow to the fetus, a process that fails in pre-eclamptic patients.
Previous research suggests that the TGF-b pathway induces ANGPTL4 expression in breast cancer cells, facilitating their metastasis to the lungs by permeabilizing the endothelium. Trophoblasts share many similarities with cancer cells and may
share factors such as ANGPTL4 to invade the arteries.
The objective of this project was to study the effect of TGF-b on ANGPTL4 expression in HTR-8/SVneo trophoblasts by using qPCR and WB. Additionally, ANGPTL4 secretion by trophoblasts was assessed by ELISA as well as the effect of ANGPTL4 on cell migration using shRNA lentiviral infection and real-time analysis in IncucyteS3.
The results of this project showed that TGF-b stimulation increased ANGPTL4 expression in trophoblasts. ANGPTL4 knock-down leads to decreased trophoblast migration. Endothelial cells cultured in conditioned medium of trophoblasts with active TGF-b signaling, were more permeable than control cells. ANGPTL4 secretion in serum from pre-eclamptic women and healthy pregnant women, assessing with ELISA, will be presented.
These results suggest that there are similarities between the tools that breast cancer cells use to mediate metastasis and the tools that trophoblasts use to invade and replace the endothelium of the maternal spiral arteries.
