A Potential New Target for the Treatment of Endometriosis

A protein called STIP-1 is found at higher levels in the blood of women with endometriosis and adenomyosis.

Key Points

Highlights:

• Higher levels of a protein called STIP1 may be linked to the development of endometriosis via the regulation of an enzyme called MMP-9.

Importance:

• The finding of this study suggests that STIP1 could be a nice therapeutic target for endometriosis.

Key results:

• The level of STP1 is significantly higher in the blood of women with endometriosis and adenomyosis compared to those without either disease.
• Both epithelial and stromal cells in surgical tissues of endometriosis and adenomyosis express STIP1 and MMP-9, a protein that plays a role in extracellular matrix remodeling.
• Knocking down the production of STIP-1 leads to a significant decrease in the production of MMP-9.
• STIP1 binds to the MMP-9 promoter region and enhances gene expression.

Limitations of the study:

• The experiments conducted using cells grown in the laboratory were performed using endometrial cancer cells because endometriotic tissue cells are hard to maintain in the laboratory. Therefore the molecular mechanisms described in this study may not be the same in non-neoplastic endometrial or endometriosis tissues.

Lay Summary

A protein called STIP1 could be facilitating the migration of endometrial tissue outside the uterus, therefore, leading to endometriosis according to a study by Taiwanese researchers.

The protein could, thus, be used as a potential therapeutic target for endometriosis. 

For the study that was published in the scientific journal PLOS One, researchers led by Dr. Tzu-Hao Wang compared women with surgically confirmed endometriosis and adenomyosis with those free from either disease. They measured the levels of STIP1 protein in the blood of the women and analyzed tissues removed with surgery regarding protein expression. STIP1 is a protein that controls the function of other proteins called heat-shock proteins that become active in times of cellular stress. It has been shown to be implicated in the development of gynecologic cancers.

They found that the levels of STP1 were significantly higher in the blood of women with endometriosis and adenomyosis before they had surgery compared to the levels in the blood of women without either disease.

They also found that both epithelial and stromal cells in surgical tissues of endometriosis and adenomyosis expressed STIP1 and MMP-9 protein. MMP9 is an enzyme that plays a role in the degradation of the extracellular matrix, the fluid in which cells as embedded. So higher levels of STIP1 could promote the remodeling of the extracellular matrix via MMP-9 and allow endometrial tissue to migrate outside the uterus leading to endometriosis. 

Interestingly, when the researchers knocked down the production of STIP1 protein in cells grown in the laboratory, they saw that the output of MMP-9 also decreased significantly suggesting that STIP1 may be controlling the output of the MMP-9 enzyme. This hypothesis was further tested with experiments where researchers have shown that STIP1 was able to bind to the region in the DNA that controls the production of MMP-9 protein and increase its production. 

“In brief, our data suggest an association between STIP1 levels and endometriosis/adenomyosis”, the researchers wrote. They added: “ If this hypothesis is proven correct, STIP1 could be used as a promising therapeutic target for this condition”.

This study is the first that shows that the overproduction of STIP1 and MMP-9 are related to the pathophysiology of endometriosis and adenomyosis.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29304094