EFFECT OF UROKINASE GENE-KNOCKOUT ON GROWTH OF MELANOMA IN EXPERIMENT
Elena Mikhaylovna FRANTSIYANTS, Irina Viktorovna KAPLIEVA, Ekaterina Igorevna SURIKOVA, Irina Valerievna NESKUBINA, Valeria Akhtyamovna BANDOVKINA, Lidiya Konstantinovna TREPITAKI, Nataliya Sergeevna LESOVAYA, Nataliya Dmitrievna CHERYARINA, Yuliya Aleksandrovna POGORELOVA, Lyudmila Anatol’evna NEMASHKALOVA
Rostov Research Institute of Oncology of Minzdrav of Russia
Keywords: нокаут по гену uPA, меланома, хроническая нейрогенная боль, половые особенности, мыши, uPA gene knockout, melanoma, chronic neurogenic pain, gender differences, mice
Abstract
The purpose of the study
was to reveal special features of the В16/F10 melanoma growth in
urokinase (uPA) gene knockout mice with and without chronic neurogenic
pain (CNP). Material and methods. The study included male and female
С57ВL/6 mice ( n = 102) and C57BL/6-Plautm1.1BugThisPlauGFDhu/GFDhu mice
with uPA gene knockout ( n = 48). Mice of the main subgroups underwent
subcutaneous transplantation of В16/F10 melanoma 2 weeks after bilateral
ligation of sciatic nerves (CNP model); mice of the same strain with
standard melanoma transplantation served as controls. Results and
discussion. Survival of uPA gene knockout mice did not differ from that
of normal animals - 1.5 times higher in females than in males ( p <
0.05), with melanoma onset in gene-deficient mice a week earlier. The
dynamics of tumor growth had pronounced gender differences: in females,
the tumor did not grow and its maximal volume prior to death was 1.0 cm3,
while tumors in males were characterized by an active growth with two
peaks of volume increase (weeks 2 and 4). Melanoma was weakly metastatic
- solitary metastases to the lungs (in females) or no metastases, but
pulmonary and heart hemorrhages were noted (in males). CNP decreased the
survival of uPA gene knockout females, as well as of normal animals,
but did not influence the survival of males; primary tumors in
gene-deficient mice appeared a few days later than in controls but their
growth was more intense, with diminished gender differences. Increased
metastasis was manifested by the initiation of metastatic lesions to the
lungs and liver in males, with maintained pulmonary hemorrhages, and by
increased number of metastatic foci in the lungs together with the
appearance of pulmonary hemorrhages in females. Conclusions. The
influence of uPA gene knockout on the course of В16/F10 melanoma differs
in male and female mice. CNP enhances malignant tumor growth,
diminishing gender differences, and activates melanoma metastasis.
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