Release of oncofetal fibronectin from human placenta

Oncofetal fibronectin (onfFN) is an extracellular matrix (ECM) protein synthesized by tumours and fetal tissue including placenta. The appearance of onfFN and other cellular FNs in cervico-vaginal secretions and maternal blood is associated with adverse pregnancy outcomes. In the current study, we used dual (maternal and fetal) perfusion of human term placentae and primary cultures of syncytiotrophoblasts (SCTs) to determine whether the human placenta releases onfFN. ELISA and Western blotting revealed that onfFN is preferentially released to the maternal perfusate in a time-dependent manner. Immunodetection with FDC-6, extra domain A (EDA) and cell binding domain-specific antibodies revealed onfFN in maternal perfusate to be a high molecular weight (>450 kDa) protein dimer, similar to that found in amniotic fluid. This suggested that onfFN was released intact from placenta and not cleaved from an ECM. In addition, a similar high molecular weight dimeric onfFN species was noted in conditioned media from cultures of SCTs. Since SCTs directly release proteins to the intervillous space, this suggests that SCTs may be a source of onfFN detected in maternal perfusate. These results indicate that onfFN is released from human placenta and thus levels in maternal sera may provide insight into placental pathophysiology.