An in vivo rat model to study epigenetic control of cell invasion.

Due to it ability to invade deep into endometrium, as well as into other tissues at ectopic sites (testis, kidney capsule), throphoblast plays an important role in shaping the future placenta. To accomplish this task, it is necessary for throphoblast cells to differentiate into highly invasive throphoblast giant cells (TGC). The behaviour of TGC during implantation resembles that of cancer cells during metastasis. In both cases, the invasive phenotype is to a large degree controlled epigenetically, by DNA methylation, with resulting gene expression silencing. DNA demethylating agents, such as 5-azacitidine (5azaC), reverse the gene expression and change cell behaviour; already used in cancer therapy, 5azaC is also useful experimentally to elucidate epigenetic pathways in normal and malignant cells. In this paper we describe an in vivo rat model of throphoblast cell invasion, in which cells are exposed to 5azaC and transplanted ectopically under kidney capsule. We conclude that temporal variation in exposure to 5azaC, such as the gestation day, affects the throphoblast cells differentiation, and thus changes their invasive properties. We suggest that this in vivo model could be useful to study steps in epigenetic control of both the placental development and cancer cell spread.