Normal endometrial stromal cells regulate survival and apoptosis signaling through PI3K/AKt/Survivin pathway in endometrial adenocarcinoma cells in vitro

ObjectiveStroma–tumor communication plays an important role in the genesis of neoplasia. In the current study, we investigated the effect of normal stromal cells on the survival and apoptosis signaling of endometrial cancer cells and further explored the possible mechanism implied in this communication.MethodsUsing primarily cultured normal endometrial stromal cells and an endometrial adenocarcinoma cell line, Ishikawa cells, we established a 2D-coculture system to observe the stromal cell–tumor cell crosstalk in endometrial carcinomas. Using methyl thiazolyl tetrazolium (MTT) assays, cell counting and colony formation assays, we analyzed the effect of stomal cells on the growth and proliferation of Ishikawa cells under different conditions. Using western blot analysis, we determined the effect of stromal cells on the activity of PI3K/AKt/Survivin signaling in Ishikawa cells under different conditions. Using immunohistochemistry analysis, we determined the expression of Survivin in normal endometria and endometrial adenocarcinomas.ResultsWe found that the paracrine factors from normal endometrial stromal cells grown on Matrigel repeatedly and significantly decreased hormone-stimulated activity of PI3K/AKt/Survivin signaling in Ishikawa cells, which were proved to be increased in endometrial adenocarcinoma and essential in hormone-induced cell growth in Ishikawa cells.ConclusionParacrine factors from normal endometrial stromal cells can inhibit hormone-stimulated cell proliferation in Ishikawa cells by regulating cell survival and apoptosis through PI3K/AKt/Survivin signaling.

► We investigated the possible molecular mechanism underlying the stroma–tumor communication in endometrial carcinomas.
► Normal stromal paracrine factors decreased hormone-stimulated activity of PI3K/AKt/Survivin signaling in Ishikawa cells.
► Endometrial stromal cells might play an important role via regulating tumor cell proliferation in the development of endometrial carcinomas.