Characterization of a TGF beta-responsive human trophoblast-derived cell line

The placenta is formed by developing trophoblast cells to facilitate fluid, gas and nutrient exchange with the mother. Inappropriate trophoblast respo nsiveness can lead to life threatening complications during pregnancy inclu ding intrauterine growth retardation, pre-eclampsia, spontaneous abortion a nd malignancy that could lead to fetal loss. Transforming growth factor bet a (TGF beta) is a multifunctional cytokine required for embryonic developme nt and is an important regulator of human trophoblast function. Although TG F beta is critical for placental and embryonic development, there are curre ntly no established TGF beta -responsive human trophoblast-derived cell lin es available to study the mechanisms by which TGF beta regulates trophoblas t function. Our studies have examined the transformed human trophoblast-der ived cell line, ED27, to determine if it is responsive to TGF beta. Our dat a indicate that TGF beta dose responsively and reversibly inhibits cell gro wth in ED27 cells and induces classic TGF beta response genes, fibronectin and plasminogen activator inhibitor 1 (PAI-1). TGF beta also induces an inh ibitor of trophoblast invasion, tissue inhibitor of matrix metalloproteinas e-1 (TIMP-1) in ED27 cells. Our studies hare identified a human trophoblast -derived cell line that parallels isolated primary human trophoblasts in th eir responses to TGF beta. This cell line may provide us with the opportuni ty to determine TGF beta -mediated responses on human trophoblast functions not previously possible. (C) 2001 Harcourt Publishers Ltd.