Influence of urokinase gene knockout on level of prekallikrein and kallikreins 1 and 14 in mice with melanoma growth against the background of pain
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The aim is to study the content of prekallikrein, kallikreins 1 and 14 (KLK-1 and KLK-14) in mice under the conditions of activation and inhibition of the B16/F10 inoculated melanoma growth.
Materials and methods
We produced a model of chronic neurogenic pain (CNP, bilateral ligation of sciatic nerves) and a model of the B16/F10 melanoma growth against the background of CNP using female/male mice of the C57BL/6 line (with normal genome, n=75) and the C57BL/6-Plautm1.1bugthisplaughfdhu/GFDhu line (with urokinase knockout (uPA), n=46). The ELISA method was used to determine the content of prekallikrein, KLK1 and KLK14 in the tumor and skin after 3 weeks of carcinogenesis against the background of CNP.
The initially high content of prekallikrein, KLK-1 and KLK-14 in the skin of intact knockout mice was found. When inhibiting the growth and metastasis of melanoma in the skin of the knockout females, noted was a further increase in the initially high level of prekallikrein and KLK1, and in the tumor in the knockout mice of both genders recorded was a lower content of all the studied enzymes. When activating the growth of melanoma in the state of CNP in the skin of C57BL/6 mice, the level of KLK1 (female) decreased and the concentration of KLK14 (female and male) increased; in the knockout mice the content of prekallikrein and KLK14 decreased, and KLK1 changed multidirectionally. The tumor demonstrated a lower prekallikrein level in all C57BL/6 mice and multidirectional changes in KLK1 and KLK14 in females and males. The tumor in the knockout animals showed a lower content of all the studied enzymes, especially pronounced for KLK14.
The content of prekallikrein, KLK1 and KLK14 varies under activating and inhibiting the growth of melanoma, the changes are of the gender-specific type. It is probable that the functions of the studied enzymes in the skin change not only in case of CNP, but also in case of urokinase deficiency. The tumor itself adapts the performance of the kallikrein-kinin system depending on the metabolic features of the tumor-bearing organism.
Elena М. Frantsiyants, Ekaterina I. Surikova, Valeriya А. Bandovkina, Irina V. Kaplieva., Irina V. Neskubina, Natalia D. Cheryarina, Viktoria V. Pozdnyakova, Oleg I. Kit. Influence of urokinase gene knockout on level of prekallikrein and kallikreins 1 and 14 in mice with melanoma growth against the background of pain. Cardiometry; Issue 17; November 2020; p.58-65; DOI: 10.12710/cardiometry.2020.17.5865; Available from: http://www.cardiometry.net/issues/no17-november-2020/influence-of-urokinase-gene