REDOX STATE OF THE ADIPOSE TISSUE AND THE TUMOR MICROENVIRONMENT IN PATIENTS WITH COLON CANCER AND THEIR RELATIONSHIPS WITH METASTASIS
- R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine
Obesity is an important factor in the development and passing of certain types of cancer, particularly the tumors of the gastrointestinal tract. Some tumors can develop and other can metastasize in the regions of anatomical accumulation of adipose tissue (AT). Hypertrophied AT in obesity is characterized by chronic inflammation. It is an important factor that affects the formation the tumor microenvironment, and therefore the course of the cancer passing. Aim. To identify the relationships between the redox state of AT and tumor microenvironment in dependence on the clinical and pathological characteristics and the presence of obesity and other signs of the metabolic syndrome in patients with colorectal cancer (CRC). Materials and methods: the samples of tumor tissues, liver, liver metastases, AT tissues (surrounding the tumor and liver), and the blood of 84 patients with CRC at II–IV stages have been studied. The experimental techniques of electron paramagnetic resonance (EPR) at liquid nitrogen temperature and Spin Traps technology, zymography in polyacrylamide gel and the immunohistochemical, biochemical, spectrophotometric and statistical analyzes were used. Results: the defects in mechanism of oxidative phosphorylation, the increase in the rate of superoxide generation and the oxidation of guanine in DNA, the activity of matrix metalloproteinases in the AT in the vicinity of tumor were associated with the corresponding characteristics of the redox state and the content of tumor-associated adipocytes (TAA) in the tumor. These characteristics determine its aggressive phenotype and are important factors in the progression of CRC. Distant metastasis was associated with i) the high rate of the superoxide generation and quantity of TAA in tumors; ii) the high rate of the superoxide generation and activity of gelatinase, and iii) the low content of NO in the tumor tissue of the AT environment and high content of free fatty acids in the blood of patients with CPC. Conclusions: the studied indicators may have a prognostic value and become the basis of new therapeutic approaches in the treatment of CRC patients with obesity and other signs of metabolic syndrome.