Abstract
The aim of this study was to assess the expression of MMP-9 and TIMP-1 in cancerous tissue as well as in the serum and plasma concentrations of these proteins in patients with laryngeal cancer and compare the results to the inflammatory reaction in healthy subjects. Twenty-seven patients who were diagnosed with laryngeal carcinoma and selected for total laryngectomy were included in the study group. MMP-9 and TIMP-1 expression in tissues was assessed using immunohistochemical assays. Immunoenzymatic ELISA methods were used to measure MMP-9 and TIMP-1 concentrations in serum and plasma. MMP-9 and TIMP-1 were identified in tumor cells and in the tumor stroma compartment, as well as in macroscopically healthy mucous membrane. MMP-9 expression was more significant in tumor stroma than in the perimatrix of the mucous membrane (p = 0.047). TIMP-1 expression was significantly higher in the matrix and perimatrix of the mucous membrane than in cancer tissue (p = 0.0093) and the tumor stroma compartment (p < 0.0001). Expression of TIMP-1 was observed more frequently in tumors without infiltrated lymph nodes (p = 0.009). Serum concentrations of MMP-9 and TIMP-1 as well as plasma TIMP-1 concentration were significantly higher in the study group than in the control group (p = 0.0004, p = 0.002, and p = 0.0001, respectively). A significantly higher TIMP-1 level in plasma was found in patients with poorly differentiated tumors compared to G1 and G2 (p = 0.046). MMP-9/TIMP-1 rate in serum was significantly higher in the study group than in the control group. The balance between the level of MMP-9 and TIMP-1 is disrupted in laryngeal cancer. The significant correlation between TIMP-1 expression and the presence of lymph node metastases, as well as that between TIMP-1 plasma concentration and stage of cancer histological differentiation, might indicate the importance of this molecule as a prognostic factor during carcinogenesis.
Highlights
Laryngeal squamous cell carcinoma (LSCC) is one of the most common Squamous cell carcinoma TIMP (SCC) of the head and neck
Inflammatory cell intrusion was statistically higher in laryngeal carcinoma than in macroscopically healthy mucous membrane surrounding the tumor (p = 0 002) (Figure 1)
This study demonstrated for the first time the tissue expression and the concentrations of Matrix metalloproteinases (MMPs)-9 and tissue inhibitor of metalloproteinases 1 (TIMP-1) in serum and plasma in patients with laryngeal carcinoma
Summary
Laryngeal squamous cell carcinoma (LSCC) is one of the most common SCC of the head and neck. Numerous studies have indicated that the extracellular matrix is the main “support” structure of the tissues, and it could be involved in the suppression of cellular migration and proliferation. The changes mediated by enzymes involved in extracellular matrix (ECM) degradation, such as metalloproteinases, may have an impact during carcinogenesis [2]. Matrix metalloproteinases (MMPs) are important proteolytic enzymes which participate in the degradation of components of the ECM and abundant macromolecules localized on the cell surface and take part in many. There is evidence that there are changes in the MMP activity in many pathological conditions, such as inflammatory diseases and cancer [3]. Degradation of the ECM by MMPs is crucial for malignant tumor development and progression, because MMPs regulate cancer cell growth and proliferation, metastasis, angiogenesis, and the immune response to cancer [4]. The activity of MMPs is strictly regulated by their inhibitors [5]
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