Gelatinases A and B and their endogenous regulators in the corpus uteri in squamous cell cervical carcinoma

Abstract

To investigate the expression of gelatinases A and B (matrix metalloproteinases (MMP 2 and MMP 9) and endogenous regulators of their activity, such as a tissue inhibitor of MMP - TIMP-2 and a Pro-MMP-9 activator - urokinase-type plasminogen activator (uPA) as factors of corpus uteri invasion in squamous cell cervical carcinoma (SCCC). The surgical material obtained after hysterectomy in patients diagnosed with SCCC was examined. RT-PCR, immunohistochemistry (IHC), and enzyme-linked immunosorbent assay were used. In SCCC, the expressions of MMP 2 and MMP 9 were found to be high not only in carcinoma of the cervix uteri but also in the corpus uteri, which makes an additional contribution to the enhanced invasive potential of tumors and may have a prognostic value. In SCCC, the expression of MMP 9 may be induced in the corpus uteri where it was absent in normal conditions. MMP 9 can serve as a marker of an invasive process. In most cases, the activity of uPA in the tumor was significantly higher than that in intact uterine tissue, and the expression of TIMP-2 did not change substantially along the entire length of a tissue band (from the vaginal wall to the uterine fundus), as evidenced by RT-PCR, and was at a low level or absent, as shown by IHC. Impaired regulation of MMP 2 and MMP 9 expressions was found not only at the gene level, but also at post-translational one. The expression of the gelatinases MMP 2, MMP 9 and regulators of their activity is aimed at increasing the tumor destructive (invasive) potential and can occur (be induced) in the intact corpus uteri tissue that is morphologically different from cervix uteri tissue with apparent participation of signaling through an epithelial-mesenchymal interaction. The induced MMP 9 can serve as a marker for invasive potential. The data indicate different tissue functions of MMP 2 and MMP 9. They are important for understanding the role of the gelatinases MMP 2, MMP 9 during carcinogenesis, can have a prognostic value, and affect a therapeutic strategy for patient management.