Influence of urokinase gene knockout on level of prekallikrein and kallikreins 1 and 14 in mice with melanoma growth against the background of pain

Автор: Frantsiyants Elena M., Surikova Ekaterina I., Bandovkina Valeriya A., Kaplieva Irina V., Neskubina Irina V., Cheryarina Natalia D., Pozdnyakova Viktoria V., Kit Oleg I.

Журнал: Cardiometry @cardiometry

Рубрика: Original research

Статья в выпуске: 17, 2020 года.

Бесплатный доступ

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. Results 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/6mice 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. Conclusion 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.

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Mice, upa knockout, b16/f10 melanoma, chronic neurogenic pain, kallikrein-kinin system, skin, tumor

Короткий адрес: https://sciup.org/148311477

IDR: 148311477   |   DOI: 10.12710/cardiometry.2020.17.5865

Список литературы Influence of urokinase gene knockout on level of prekallikrein and kallikreins 1 and 14 in mice with melanoma growth against the background of pain

  • Yakhno NN, Kukushkin ML. Chronic pain: med¬ico-biologic and sotsio-economic aspects. An¬nals of the Russian academy of medical sciences. 2012;67(9):54-8. [in Russian]
  • Price TJ, Ray PR. Recent advances toward under¬standing the mysteries of the acute to chronic pain tran¬sition. Current Opinion in Physiology. 2019; (11):42-50. https://doi.org/10.1016/j.cophys.2019.05.015
  • Kit OI, et al. Some mechanisms of increasing ma¬lignancy of B16/F10 melanoma in female mice with chronic pain. Russian Journal of Pain. 2017;2(53):14-20. [in Russian]
  • Kit OI, et al. Influence of chronic neuropathic pain on the course of malignant В16/F10 melanoma in male mice. University news. North-Caucasian region. Natu¬ral sciences series. 2019;1(201):106-11. [in Russian]
  • Frantsiyants EM, et al. Effect of urokinase gene-knockout on growth of melanoma in experiment. Siberian Scientific Medical Journal. 2019;39(4):62-70. https://doi.org/10.15372/SSMJ20190408 [in Russian]
  • Almholt K, et al. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice. Int J Cancer. 2005;113(4):525-32. https://doi.org/10.1002/ijc.20631.
  • Breuss JM, Uhrin P. VEGF-initiated angiogen¬esis and the uPA/uPAR system. Cell Adh. Migr. 2012;6(6),535-540. https://dx.doi.org/10.4161%2F¬cam.22243
  • Dergilev KV, et al. Multifaced Roles of the Uroki¬nase System in the Regulation of Stem Cell Niches. Acta naturae. 2018;10(4):19-32.
  • Lund LR, et al. Plasminogen activation indepen¬dent of uPA and tPA maintains wound healing in gene-deficient mice. EMBO J. 2006; 25(12):2686-2697. https://doi.org/10.1038/sj.emboj.7601173
  • Dong Y, et al. Activation of membrane-bound proteins and receptor systems: a link between tis¬sue kallikrein and the KLK-related peptidases. Biol. Chem. 2014; 395(9): 977–90. https://doi.org/10.1515/hsz-2014-0147
  • Kryza T, et al. The kallikrein-related peptidase family: dysregulation and functions during cancer progression. Biochimie. 2016; 122:283-99. https://doi.org/10.1016/j.biochi.2015.09.002
  • Yam MF, et al. General Pathways of Pain Sensation and the Major Neurotransmitters Involved in Pain Regulation. Int J Mol Sci. 2018; 19(8):2164. https://doi.org/10.3390/ijms19082164
  • Brusco I, et al. Kinins and their B1 and B2 recep¬tors are involved in fibromyalgia-like pain symptoms in mice. Biochemical Pharmacology. 2019; 168: 119-32. https://doi.org/10.1016/j.bcp.2019.06.023
  • Kit OI, et al. Influence of neurogenic chronic pain on indicators of kallikreinkinin system in skin of fe-male mice in dynamics of В16/F10 melanoma devel¬opment. Medical Herald of the South of Russia. 2018; 9(2):51-60. https://doi.org/10.21886/2219-8075-2018-9-2-51-60 [in Russian]
  • Borgoño CA, et al. Expression and functional characterization of the cancer-related serine protease, human tissue kallikrein 14. J. Biol. Chem. 2007; 282: 2405-22. https://doi.org/10.1074/jbc.M608348200
  • Nauroy P, Nyström A. Kallikreins: Essential epi¬dermal messengers for regulation of the skin micro-environment during homeostasis, repair and disease. Matrix Biology Plus. 2020; 6–7: 100019. https://doi.org/10.1016/j.mbplus.2019.100019
  • Matus CE, Bhoola KD, Figueroa CD. Kinin B1 Receptor Signaling in Skin Homeostasis and Wound Healing. Yale J Biol Med. 2020;93(1):175-85.
  • Koumandou VL, Scorilas A. Evolution of the plas¬ma and tissue kallikreins, and their alternative splic¬ing isoforms. PLoS One. 2013; 8(7): e68074.
  • Fink E, et al. Cellular expression of plasma prekallikrein in human tissues. Biol Chem. 2007; 388(9):957-63. https://doi.org/10.1515/BC.2007.104
  • Mogil JS. Sex differences in pain and pain inhi¬bition: multiple explanations of a controversial phe-nomenon. Nat Rev Neurosci. 2012;13(12):859-66. https://doi.org/10.1038/nrn3360
  • Mapplebeck JC, Beggs S, Salter MW. Sex dif¬ferences in pain: a tale of two immune cells. Pain. 2016;157 Suppl 1:S2-6. https://doi.org/10.1097/j.pain.0000000000000389
  • Kalinska M, et al. Kallikreins–the melting pot of activity and function. Biochimie. 2016; 122:270-82. https://doi.org/10.1016/j.biochi.2015.09.023
  • Pavlopoulou A, et al. Evolutionary History of Tissue Kallikreins. PLoS One. 2010; 5(11): e13781. https://doi.org/10.1371/journal.pone.0013781
  • Fuhrman-Luck RA, et al. Proteomic and other analyses to determine the functional consequences of deregulated kallikrein-related peptidase (KLK) expression in prostate and ovarian cancer. Pro¬teom. Clin. Appl. 2014; 8(5–6): 403-15. https://doi.org/10.1002/prca.201300098
  • Delaunay T, et al. Aberrant expression of kallikrein-related peptidase 7 is correlated with hu¬man melanoma aggressiveness by stimulating cell mi¬gration and invasion. Mol Oncol. 2017;11(10):1330-47. https://doi.org/10.1002/1878-0261.12103
  • Stefanini AC, da Cunha BR, Henrique T, Ta¬jara EH. Involvement of Kallikrein-Related Peptidases in Normal and Pathologic Process¬es. Dis Markers. 2015;2015:946572. https://doi.org/10.1155/2015/946572
  • Yiu WH, et al. Tissue kallikrein mediates pro-in¬flammatory pathways and activation of protease-ac-tivated receptor-4 in proximal tubular epithelial cells. PloS One. 2014; 9(2): e88894. https://doi.org/10.1371/journal.pone.0088894
  • Gao L, Chao L, Chao J. A novel signaling pathway of tissue kallikrein in promoting keratinocyte migration: activation of proteinase-activated receptor 1 and epider¬mal growth factor receptor. Exp. Cell Res. 2010;316(3): 376-89. https://doi.org/10.1016/j.yexcr.2009.10.022
  • Kryza T, et al. The molecular function of kallikrein-related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer. Mol On¬col. 2020;14(1):105-28. https://doi.org/10.1002/1878-0261.12587
  • Smith HW, Marshall CJ. Regulation of cell sig¬nalling by uPAR. Nat. Rev. Mol. Cell. Biol. 2010; 11(1):23‒36. https://doi.org/10.1038/nrm2821
  • Klimovich PS, Semina EV. Mechanisms of Partic¬ipation of the Urokinase Receptor in Directed Axo¬nal Growth. Mol. Biol. 2020; 54: 89–98. https://doi.org/10.1134/S0026893320010094
  • Beaufort N, et al. Interplay of human tissue kallikrein 4 (hK4) with the plasminogen activation system: hK4 regulates the structure and functions of the urokinase-type plasminogen activator receptor (uPAR). Biological Chemistry. 2006; 387(2):217-22.
  • Figueroa CD, Molina L, Bhoola KD, Ehrenfeld P. Overview of tissue kallikrein and kallikrein-re¬lated peptidases in breast cancer. Biol Chem. 2018;399(9):937-57. https://doi.org/10.1515/hsz-2018-0111
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