Association of matrix metalloproteinase-3 with transforming growth factor-β1 mediated increased cellular invasion in ovarian endometriosis

Endometriosis is an estrogen-dependent gynecological disease, where ectopic growth of endometrial tissues causes severe pain and infertility. The pathophysiology of endometriosis involves cellular invasion and transitions such as epithelial-mesenchymal transition (EMT). Matrix metalloproteinase (MMP)-3 and transforming growth factor (TGF)-β pathway are two important regulators of the process. In this report, we studied 12 control women without endometriosis and 24 women with ovarian endometriosis (12 early and 12 late stages) for evaluation of serum and tissue levels of MMP3 and TGFβ1. Serum levels of MMP3 and TGFβ1 were significantly elevated in patients with endometriosis compared to control women. Late stage (III and IV) endometriosis patients displayed significantly higher levels of serum MMP3 and TGFβ1 than early stage (I and II) patients. We found a positive correlation between serum MMP3 and TGFβ1 levels. Ectopic endometriotic tissues exhibited higher MMP3 expressions as compared to eutopic endometrium and were increasingly expressed with severity of the disease. In vitro studies using Chinese hamster ovarian epithelial (CHO) cells found TGFβ1 treatment upregulated MMP3 levels. TGFβ1 treatment promoted cellular invasion of CHO cells in a MMP dependent manner. Present study highlights an association of MMP3 in TGFβ1-mediated promotion of cellular invasion in endometriosis.