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

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 NFkappaB 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 NFkappaB 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 NFkappaB 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 NFkappaB-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.