The role of NUMB in human extravillous trophoblast cell migration and survival

Abstract

Placental growth and development depend on highly regulated extravillous trophoblast (EVT) function, such as proliferation, migration and invasion. NUMB has been reported to playa role in cell differentiation and proliferation. An established cell line (HTR8/SVneo) was used as a model to study the role of NUMB in invasive extravillous trophoblast cell migration and survival in the human placenta. Immunofluorescence showed the presence of NUMB at the plasma membrane and the cytoplasmic region in HTR8/Svneo cells. NUMB isoform 1 significantly increased EVT migration while NUMB knockdown decreased the rate of migration as compared to the negative control. Overexpression of Numb 1,3,4 and 8 did not influence cellular viability whereas Numb 2 overexpression decreased trophoblast viability significantly. We have demonstrated for the first time that Numb is expressed in human invasive extravillous trophoblasts and that its role is isoform-dependent. Dysregulation of NUMB expression/function may playa role in placental pathologies such as preeclampsia and IUGR.