Influence of urokinase gene knockout on tissue levels of biogenic amines in mice with melanoma.

Abstract

e22109 Background: The plasminogen activation system and biogenic amines are involved in melanoma pathogenesis, but currently, the mutual influence of the components of these systems on each other is unknown. The purpose of the study was to reveal the dynamics of biogenic amines in the brain and intact and tumorous skin (B16/F10 melanoma) in C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice with uPA gene knockout. Methods: The study included male and female C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu mice, n = 38; the comparison group included C57BL/6 mice without uPA gene knockout, n = 61. Melanoma was transplanted under the skin of the back. Levels of biogenic amines were measured in tissues taken in week 3 of carcinogenesis by ELISA using standard test systems (Cusabio, China). Results: The total content of biogenic amines was elevated in tissues of intact C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice: in the skin – due to the noradrenaline (NA) rise by 4.8 times in males and by 4.9 times in females, histamine (H) – by 3.6 times in males and 1.6 times (p < 0.05) in females, serotonin (5HT) by 3.4 times in males and 8.3 times in females; in the brain – due to the NA rise by 3.5 times in males and 3.2 times in females, dophamine by 2.1 times in males and 2.9 times in females, while H levels declined. Distinctive features of the melanoma development in C57BL/6-PlautmI.IBug-ThisPlau6FDhu/GFDhu mice included: lower levels of adrenaline with high NA concentrations and an enhanced synthesis and inactivation of 5HTin the brain. The content of catecholamines in the tumor nodes was the same as in C57BL/6 mice, with a high concentration of H recorded in the tumor and skin, together with a high 5HT level in the skin. Conclusions: The uPA gene knockout limits the development of stress at the central regulatory and peripheral effector levels, and modulates the immune antitumor response by increasing serotonergic mediation in the brain and increasing serotonin and histamine levels in the skin of mice with B16/F10 melanoma.