Matrix metalloproteinase-11 as a potential tumor marker of uterine leiomyoma

Objective. To evaluate the specific activity of serum immunoglobulins against the matrix metalloproteinase-11 (MMP11) protein in the groups of mothers of many children and patients with uterine fibroids.

Materials and methods. A cDNA fragment containing the MMP11 gene from a cell line with increased expression of this protein was cloned. Recombinant human MMP11 protein produced in E. coli was purified and used to investigate the limit titer of antibodies in blood sera of patients using indirect ELISA. Donor blood serum samples (100 samples) were collected from the patients undergoing treatment at V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology. Informed consent to participate in the study was obtained from the patients. To investigate the immunological activity of sera against the MMP11 protein, four groups of patients were formed. Group 1 consisted of women without diagnosed fibroids who had a history of five or more successful pregnancies. Group 2 consisted of women with fibroids, who also had five or more successful pregnancies. Group 3 included women with recurrent fibroids. Group 4 was the control group of men. An expression construct containing the MMP11 gene was inserted into the E. coli genome. As a result, preparative protein was obtained in sufficient amount to investigate its reaction with antibodies in the blood sera of different patient groups.

Results. Western blot analysis showed that the blood sera of women without fibroids, who had many children, contain antibodies to the MMP11 protein, that provided grounds for a broader study of the immunological reactivity of the blood sera in different groups of patients against this protein. In gentral, the highest protein reactivity was shown in the sera of women with many children. However, the average value for the group of women with fibroids, who had many childeren, was higher, but not statistically significant. In patients with fibroids the reactivity was lower than in group 1, and the lowest was in the control group of men. At the same time, statistical analysis showed significant differences between the groups using different dilutions, that is, there was a dose dependence of the immunological response. The obtained results confirm statistically significant differences in serum reactivity between the studied groups. At the same time, the identified dose-dependent dynamics corresponds to the expected immunological patterns.

Conclusion. Our study showed that the MMP11 protein reacts with antibodies from the sera of different patient groups. At the same time, higher immune response to this protein was found in the group of mothers with many children. The MMP11 protein may further be useful in the development and testing of new targeted preventive therapy for uterine fibroids.