THE EPITHELIAL-MESENCHYMAL TRANSITION IN THE TUMORS: MOLECULAR FEATURES OF PATHOGENESIS
Abstract
The aim of our study is: to investigate the peculiarities of antioxidant system enzymes activity and iron content in tumors of various localizations, to determine a possible relationship between the metabolic features and epithelial-mesenchymal transition (EMT) development.
Material and Methods. We studied 25 samples of non-small cell lung cancer, 10 samples of gastric cancer and 12 samples of colon cancer T3N0-хM0 stage. The activity of antioxidant system enzymes – superoxide dismutase (SOD) and glutathione peroxidase (GPO) – was studied spectrophotometrically in tumor homogenates. In parallel, a comparative determination of iron content in tissues and blood erythrocytes was performed by atomic emission spectrometry.
Results. For tumors of non-small cell lung cancer, gastric and intestinal adenocarcinomas their metabolic heterogeneity was established. By the results of analysis in morphologically homogeneous tumors of the same localization we detected clusters of tumors characterized by increased activity of superoxide dismutase, decreased activity of glutathione peroxidase (negative relation with pathology (ρ = – 0,47, p < 0,05)). The implementing EMT tumors of the studied localizations are characterized by an imbalance in the activity of SOD and GPO, which leads to an increase in the levels of hydrogen peroxide and the realization of its stimulating transition effects. The aggressive phenotype of carcinomas formation is also promoted by increased iron levels in tumor tissues as compared to non-transformed tissues (p = 0.03). There was found an inverse relationship between the increased iron content in the tumor and its decreased content in erythrocytes of the blood flowing from the affected organ (Spearman correlation index ρ = -0.66). Since hydrogen peroxide stimulates the ability of proteins to release ionized iron, we assume that erythrocytes can become a source of iron for tumor tissues.
Conclusion. Molecular features of EMT pathogenesis may be the combined increase of hydrogen peroxide and iron ions levels in the tumor. Since hydrogen peroxide stimulates the ability of proteins to release ionized iron, we assume that red blood cells can become a source of iron for tumor tissues.
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