Endometriotic epithelial cells induce MMPs expression in endometrial stromal cells via an NFкB-dependent pathway

Abstract

Objective. To explore the stroma–epithelium interactions in endometriosis and to identify the possible signalling pathways involved in this cross-talk.Design. Laboratory study via primary cultured endometrial stromal and epithelial cells.Setting. University Hospital.Patients. Fifteen patients with endometriosis confirmed by histopathology were recruited in the study, and 12 women free of endometriosis were used as control group.Intervention(s). Specific NFкB inhibitor 1-Pyrrolidinecarbodithioic acid ammonium salt (PDTC) was used in cell cultures.Main outcome measure(s). The expression and secretion of MMP-2, MMP-9, TIMP-1, TIMP-2 and the DNA-binding activity of NFкB in normal endometrial stromal cells or in co-cultures with normal or endometriotic epithelial cells from patients with endometriosis.Result(s). Endometrial epithelial cells induced MMP-9 and MMP-2 expression in normal stromal cells in vitro. In co-cultures with endometriotic epithelial cells, normal endometrial stromal cells expressed and secreted higher MMP-2 (p < 0.05) and MMP-9 (p < 0.05). Specific inhibition of NFкB pathway in stromal cells abolished this induction effect by epithelial cells.Conclusion(s). Endometriotic epithelial cells induce MMPs expression and secretion in normal endometrial stromal cells via an NFкB-dependent pathway in vitro. This cross-talk between epithelial cells and stromal cells may facilitate the implantation and extension of the ectopic foci and favour the development of the disease.