Researchers showed for the first time that a protein called trefoil factor 3, or TFF3, can be found in higher concentrations in the peritoneal cavity of endometriosis patients. This suggested that TFF3 may be linked to inflammatory processes and the overall progression of endometriosis.
TFF3 is expressed in different tissues, including the uterus, and is associated with tissue recovery and cell proliferation and differentiation. This protein was found to be upregulated in many cancers, including endometrial cancer, and in experimental cell lines of estrogen-responsive breast cancer after estrogen treatment. TFF3 was shown to be involved in inflammatory processes and immune responses, but also plays a key role in maintaining the tissues’ surface integrity.
As endometriosis is an estrogen-dependent disease characterized by inflammatory processes, the authors of the study hypothesized that TFF3 could be involved in the remodeling processes of the endometrial tissue.
They collected peritoneal fluid (PF) from the peritoneal cavity, the area between the peritoneum — the external thin layer of the abdomen — and the organs of 34 women with confirmed endometriosis and from a control group of 16 women without the disease.
The authors found that endometriosis patients had increased levels of TFF3 in their PF when compared to the control group. This result was further confirmed in animal models of endometriosis.
They also found that the levels of this protein were positively correlated with several markers commonly elevated in endometriosis, such as cancer antigen (CA) 125, CA 19-9, IL-8, MCP-1, and MMP-7. Some of these markers are associated with inflammatory processes and others with tissue remodeling, suggesting that TFF3 may participate in these processes in endometriosis.
“The correlation of elevated TFF3 levels with these markers might be one hint for the involvement of TFF3 in the pathogenesis of endometriosis,” the authors wrote.
Analysis of blood levels of TFF3 in 80 patients with endometriosis and 44 controls without the disease showed no differences between the groups. Because it was not detected, this protein could not qualify as a potential diagnostic marker for endometriosis, the authors said.
However, the authors found that the blood levels of TFF3 would vary accordingly with the menstrual cycle. This can be explained by its pro-inflammatory activity and hormone-dependent responsiveness.
Overall, results of this study suggest that TFF3 may be involved in tissue remodeling affecting the endometrium and the surrounding peritoneal environment, favoring the development and progression of endometriosis.
“Additional studies are needed to determine the exact role of TFF3 in the development and progression of endometriosis and its regulation throughout the menstrual cycle of women,” the authors concluded.