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Abstract
Tumor vascularisation is an important aspect of melanoma growth. The system of urokinase and its receptor (uPA/uPAR system) plays an important role in tumor metastasis which makes it an attractive therapeutic target. Our purpose was to study the dynamics of angiogenic growth factors in male and female uPA gene-knockout mice (C57BL/6-PlautmI.IBug-This Plau6FDhu/GFDhu strain) during the growth of experimental B16/F10 melanoma developing in animals with chronic neurogenic pain (CNP). Material and methods. Group 1 included С57BL/6 mice of both genders, n=75; group 2 - C57BL/6-Plautm1.1Bug-This PlauGFDhu/GFDhu mice (uPA gene knockout), n=46. Levels of VEGF-A, VEGF-C, sVEGF-R1, and sVEGF-R3 were determined by ELISA (CUSABIO BIOTECH Co.,Ltd., China). Results. uPA gene-knockout mice of both genders with melanoma and CNP showed survival similar to animals with a normal genome; however, the period to tumor onset was longer in such animals (by 2.6 times on average), and the volume of primary tumors was on average 2.2 times higher. The concentration of angiogenesis factors in skin and tumor samples was lower in male and female uPA gene-knockout mice with experimental B16/F10 melanoma and CNP, compared to animals without the knockout. Conclusions. uPA gene knockout inhibits VEGF in males, unlike females, and chronic neurogenic pain stimulates the formation of this factor in knockout animals of both genders which confirms triggering of urokinase-independent pathway of angiogenesis activation under the influence of CNP.
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