[Matrix metalloproteinases and their endogenous regulators in squamous cervical carcinoma (review of the own data)].

Expression of matrix metalloproteinases (MMPs) and their endogenous regulators has been investigated in squamous cervical carcinoma (SCC). The study included (i) immortalized fibroblasts (IF) and three clones of fibroblasts transformed by oncogene E7 HPV-16 (TF); (ii) cell lines associated with HPV-16 and HPV-18; (iii) tumor tissue samples from patients with SCC, associated with gene E7 HPV-16. Transfection of fibroblasts with the E7 HPV16 oncogen was accompanied by induction of collagenase (MMP-1, MMP-14) and gelatinase (MMP-9) gene expression and the increase in catalytic activity of these MMP, while gelatinase MMP-2 expression remained unchanged. Expression of MMP-9 was found only inTF. MMP-9 may serve as a TF marker. In TF expression mRNA TIMP-1 was decreased. The level of free endogenous inhibitors in TF was significantly lower then the level in IF. Expression MMP correlated with the tumorigenic potential of TF. Invasive potential of cell lines associated with HPV18 (HeLa and S4-1) was more pronounced than that of cell lines associated with HPV16 (SiHa and Caski). The cell lines differed substantially in the level of expression of MMPI and their endogenous regulators. In most cell lines mRNA levels of collagenases MMP-1 and MMP-14 and the activator (uPA) increased, while gelatinase MMP-2 mRNA and tissue inhibitors mRNAs changed insignificantly. MMP-9 expression in cell lines was not detected. Results of studies on these cell lines suggest existence of an imbalance in the system enzyme/inhibitor/activator, that increases destructive potential of these cells. The study of expression of MMP and their endogenous regulators performed using SCC tumor samples associated with HPV16 has shown that the invasive and metastatic potentials of tumor tissue in SCC is obviously determined by the increase of expression of collagenases MMP-1, MT1-MMP and gelatinase MMP-9, decreased expression of inhibitors (TIMP-1 and TIMP-2), and to a lesser extent to increased expression of MMP-2. MMP-1 and MMP-9 can serve as markers of invasive and metastatic potential of the SCC tumor. In adjacent to the tumor normal tissue revealed a significant expression of MMP-1,-2,-9.

[Matrix metalloproteinases 2 and 9, their endogenous regulators, and angiotensin-converting enzyme in cervical squamous cell carcinoma].

OBJECTIVE: to investigate the specific features of the expression of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), tissue inhibitor of metalloptoteinase 2 (TIMP-2), urokinase-type plasminogen activator (uPA), and angiotensin-converting enzyme (ACE) in cervical squamous cell carcinoma (CSCC). MATERIAL AND METHODS: The samples of tumor tissue and morphologically normal tissue adjacent to the tumor were investigated. Enzymatic assays applying specific substrates, as well as zymographic and immunohistochemical studies were used. RESULTS: The invasive potential of CSCC has been established to be substantially influenced by the increased expression of MMP-9 and uPA and by the decreased expression of TIMP-2, as well as to a lesser extent by a change in MMP-2 expression. MMP-9 may serve as a marker for invasive growth. Enhanced ACE activity in cancer confirms the involvement of this enzyme in tumor progression. The morphologically normal tissue adjacent to the tumor shows the substantial expression of MMP-2 and MMP-9 and in some cases the enhanced activity of uPA and ACE, which makes an additional contribution to the increased invasive potential of tumor. CONCLUSION: The findings are important in understanding the mechanisms of cancer progression and may affect therapeutic strategies for the patient.