Matrix Metalloproteinase-2 and -9, Lactate, and Malate Dehydrogenase and Lipid Peroxides in Sera of Patients with Colorectal Carcinoma

Abstract

Matrix metalloproteinases (MMPs) are involved in tumour invasion and metastasis of colorectal carcinoma. Oxidative stress represents one of the possible mechanisms that activate inactive MMPs. Oxidative stress increases lipid peroxidation, which causes impaired membrane permeability and leakage of lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) into circulation. Our aim was to assess the activity of MMP-2 and MMP-9 and its relation to the parameters of oxidative stress and membrane damage markers in patients with different TNM (tumour, lymph nodes, metastasis) stages of colorectal carcinoma. MMP-2 and -9 activities were evaluated by gelatin zymography. Oxidative stress was examined by quantifying serum malondialdehyde (MDA) concentration. LDH and MDH activities were determined spectrophotometrically. The activities of MMP-2 and -9 were significantly higher in the sera of colorectal carcinoma patients when compared to healthy subjects. There was a stage-dependent increase in relative MMP-2 activity compared to the overall serum gelatinolytic activity. The activity of MMP-9 was the highest in TNM III. The MDA concentration and the LDH and MDH activities were significantly higher in colorectal carcinoma patients than in controls, while LDH and MDH activities were stage dependent. There was significant correlation between serum MMP-2 and LDH activity in TNM II, III and IV patients. A stage-dependent increase of LDH and MDH activity was observed. We highlight here that MMP-9 could be a 100% sensitive marker of TNM stage III of colorectal carcinogenesis. In this study it was shown for the first time that gelatinolytic activity in colorectal carcinoma is associated with redox imbalance.