Calreticulin has opposing effects on the migration of human trophoblast and myometrial endothelial cells

Calreticulin is a calcium binding, endoplasmic reticulum resident protein best known for its roles in intracellular calcium homeostasis and the quality control processes of the endoplasmic reticulum. There is evidence for a range of activities for calreticulin outside the endoplasmic reticulum, including in the cytosol, on the surface of different cells types and in the extracellular matrix. Recent evidence indicates that human pregnancy is a condition of elevated circulating calreticulin. Calreticulin was increased in the plasma of women throughout pregnancy compared to the non-pregnant state. Calreticulin was also further increased during the hypertensive disorder of human pregnancy, pre-eclampsia. To clarify the roles of circulating calreticulin in pregnancy and pre-eclampsia, the aim of this study was to determine the effects of exogenous calreticulin on two cell types that are relevant to normal human pregnancy and to pre-eclampsia. Human primary myometrial microvascular endothelial cells (UtMVEC-Myo) and the human trophoblast cell line, HTR8/SVneo, were cultured with exogenous calreticulin at concentrations (2 μg/ml and 5 μg/ml) comparable to that measured in maternal blood. The higher concentration of calreticulin significantly increased the migration of the UtMVEC-Myo cells, but significantly reduced the migration of the HTR8/SVneo cells. In the presence of only FGF, FBS and antibiotics calreticulin at 5 μg/ml significantly reduced the number of UtMVEC-Myo cells during in vitro culture for 120 h. These results demonstrate that exogenous calreticulin can alter both HTR8/SVneo and UtMVEC-Myo cell functions in vitro at a (patho-) physiologically relevant concentration. Increased calreticulin may also contribute to altered functions of both cell types during pre-eclampsia.