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

Gynecol Endocrinol. 2010 Jun;26(6):456-67. doi: 10.3109/09513590903366988.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Endometriosis / metabolism*
  • Endometriosis / physiopathology
  • Endometrium / metabolism*
  • Epithelial Cells / metabolism*
  • Female
  • Humans
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinases / biosynthesis*
  • Middle Aged
  • NF-kappa B / metabolism*
  • Signal Transduction
  • Stromal Cells / metabolism*

Substances

  • NF-kappa B
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9