Units of fibrinolytic system in mice with urokinase gene knockout in presence of growing B16/F10 melanoma

Purpose of the study. Was to reveal the effect of urokinase gene knockout in male and female mice with transplanted  B16/F10 melanoma on the functions of the fibrinolytic system units.

Materials and methods. Male and female mice were used: main group with genetically modified mice C57BL/6-Plautm1. 1Bug – ThisPlauGFDhu/GFDhu (uPA-/-); control group with С57Bl/6 (uPA+/+) mice. B16/F10 melanoma was transplanted by the standard methods to the animals, and levels of plasminogen (PG), plasmin (PAP), urokinase receptor uPAR, content (AG) and activity (act) of uPA, t-P A and PAI-I were measured with ELISA (Cussabio, China) in 10 % tumor homogenates and peritumoral area after 3 weeks of tumor growth.

Results. The activity and levels of urokinase in intact uPA-/- animals were significantly (by 100–860 times) inhibited, compared to uPA+/+, but uPAR levels were unchanged in females and were 1.9 times lower in males. PAP levels in uPA-/- mice were 2.1–4.2 times higher than in uPA+/+ animals. The growth of B16/F10 melanoma in uPA-/- mice was slower and metastasizing was suppressed, but their survival was not improved. The dynamics of changes in components of the fibrinolytic system in presence of melanoma growth differed in uPA-/- mice, compared to uPA+/+ animals: PAP levels in tumor samples decreased by over 2 times, uPA levels and activity were not increased, PAI was practically unchanged, but activity of t-P A elevated by 3.8–8.2 times, as well as in uPA+/+ mice.

Conclusion. Despite the suppression of the growth and metastasis of the primary tumor nodes in uPA-/- mice, their average survival was not improved, which indicates that the mechanisms of tumor are complex and there are alternative biological pathways supporting melanoma to survive in conditions of the urokinase gene knockout.

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