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

Abstract

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). 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. 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. The findings are important in understanding the mechanisms of cancer progression and may affect therapeutic strategies for the patient.