MATRIX METALLOPROTEINASES-2 AND -9 AS REDOX-DEPENDENT MARKERS OF BREAST CANCER METASTASIS

Ganusevich I.I., Virko S.V., Burlaka A.P.

• R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv, Ukraine

Determining prognostic factors is a key point for assessing the aggressiveness of breast cancer (BC), individual prognosis and probable response to treatment. MMP-2 and -9 (gelatinases) are redox-dependent molecules that provide proteolytic degradation of the intercellular matrix and signaling at each stage of the metastatic cascade. Aim: to investigate the relationship between redox-dependent activation of gelatinases and metastasis, levels of MMP-2 and -9 activity in the adipose tissue (AT) of obese breast cancer patients and in the serum of breast cancer patients with a different hormone receptor status. Object and methods: blood, tumor and adipose tissues of 116 patients with stage I-IV breast cancer were studied. Methods of zymography in polyacrylamide gel, electron-paramagnetic resonance, statistical were used. Results: superoxide radicals (SR), which control the activity of gelatinases, are involved in the destruction regulation of the intercellular matrix during the progression of breast cancer. The levels of the SR generation rate and the activity of MMP-2 and -9 in the tumor correlate with each other, as well as with the stages and regional metastasis of breast cancer. The levels of gelatinase activity in the breast AT in patients with breast cancer of the basal molecular subtype with obesity depend on its volume and distance from the tumor. We detected violations of the redox state of neutrophils and the functioning of gelatinases in the serum of patients with breast cancer of reproductive age, which depend on the hormonal status of women, are manifested by increased levels of SR and MMP-9 activity in ER (-)/PR (-) tumor status and may affect the course of the disease and the survival of patients. Conclusions: indicators of gelatinase activity, determined in tumor and blood, are promising markers of breast cancer progression, in particular for overweight patients and/or for patients of reproductive age with a certain hormonal status.