Expression pattern of progranulin in the human placenta and its effect on cell proliferation in the choriocarcinoma...

Expression of the glycoprotein progranulin has been recently identified in rodent trophoblast cells during early embryonic development. The aim of our study was to describe the expression pattern of progranulin in human placental tissue specimens by immunostaining. We further analyzed the influence of progranulin on invasion and migration of isolated first trimester villous trophoblast cells. The effect of progranulin on cell proliferation was investigated using the human choriocarcinoma derived cell lines BeWo and Jeg-3. Cells were tested with recombinant human progranulin at various concentrations (0.1, 0.2 and 1.0 µg/ml). The strongest expression of progranulin was observed in the villous trophoblast cells, particularly in the syncytiotrophoblast. The intensity of staining in these cells was higher in the first trimester than in the third trimester. In contrast, the staining of the extravillous trophoblast cells and of the villous and decidual stroma was only weak. Using an ELISA technique, we also detected progranulin in amniotic fluid of the early second trimester. Isolated human first trimester trophoblast cells also expressed and secreted progranulin. Progranulin significantly stimulated the cell proliferation of BeWo cells, but it did not influence the amount of trophoblast cell migration and invasion in vitro. Furthermore, it did not promote the cell proliferation of Jeg-3 cells. Our results suggested that progranulin, although it is mainly synthesized and secreted by villous trophoblast cells, may not primarily act on the villous trophoblast cells in a paracrine or autocrine manner. The observed effect of progranulin on cell proliferation in BeWo cells may indicate a growth stimulating effect also on the small part of proliferating extravillous trophoblast cells during placental development.