Insulin-Like Growth Factor (IGF)-I Stimulates Proliferation and Migration of Mouse Ectoplacental Cone Cells, While IGF-II Transforms them into Trophoblastic Giant Cells in Vitro1

We examined the effects of a 10.5-day placental extract and various growth factors (insulin-like growth factor [IGF]-1, IGF-II, epidermal growth factor [EGF], basic fibroblast growth factor [b-FGF], and transforming growth factor-alpha [TGF-alpha]) on proliferation, migration, and transformation of mouse ectoplacental cone (EPC) cells in vitro. Both the 10.5-day placental extract and IGF-I increased the surface area of the EPC cell colony and strongly stimulated the uptake of bromodeoxyuridine (Brd-U) as well as the migratory activity of EPC cells on the plastic culture dish. Such effects of 10.5-day placental extract were partly inhibited by the addiction of anti-IGF-I antibody. On the other hand, IGF-II did not significantly affect proliferation and migration of EPC cells, but increased the number of cells having a large nucleus (trophoblastic giant cells; TGCs) per EPC and enlarged the ploidy levels of EPC cells. Histochemical staining with succinyl wheat germ agglutinin (s-WGA), an in situ marker for secondary TGCs on Day 10.5 post coitum revealed that IGF-II or the placental extract induced the expression of s-WGA-binding glycoproteins in the TGCs in vitro. The effects of IGF-II or placental extracts were also inhibited by anti-IGF-II monoclonal antibody. No appreciable effect was found in the EPCs cultured with TGF-alpha, whereas b-FGF and EGF promoted migratory activity of the cells. The present study indicates that IGFs or IGF-like substances may be present in the mouse placenta, that IGF-I may promote the proliferation and migration of EPC cells, and that IGF-II may induce the transformation of EPC cells into TGCs in vitro.