Abstract
Aim: comparative analysis of plasmin, plasminogen (PG), urokinase PG activator (uPA) and its receptor (uPAR) in tissues of malignant tumors and intact skin of С57ВЬ/6 mice of both genders in В16/F10 melanoma reproduced in chronic neurogenic pain (CNP). Methods: The study was performed on 130 mice and В16/ F10 melanoma cell line. Levels of uPA-antigen (uPA-AG) and uPA-activity (uPA-act), uPAR, PG, PAP (plasmin-a2-antiplasmin complex) were determined by ELISA. Statistics: the Statistica 10 program. Results. CNP-induced depletion of the content and activity of uPA was maintained in the skin and tumors after melanoma transplantation. Elevation of uPAR in females under the influence of CNP after the transplantation normalized at the terminal stage only; decreased levels of uPAR in males were maintained during the whole experiment. Elevation of PAP in females with CNP was maintained in the skin and tumors after the transplantation, and in males it was less marked. CNP affected the time of development of transplantable В16/F10 melanoma in female and male С57ВL/6 mice, changed gender differences typical of the standard tumor transplantation, decreased the period prior to the development of metastases, increased their number and extended localization. Conclusions. The study confirmed involvement of plasmin and uPAR in the formation of В16/F10 melanoma in CNP with changing gender priorities in development and spread of the process.
References
Яхно Н.Н., Кукушкин М.Л. Хроническая боль: медикобиологические и социально-экономические аспекты. Вестник РАМН. 2012; 9:54-58.
Leppert W, Zajaczkowska R, Wordliczek J, Dobrogowski J, Woron J, Krzakowski M, Pathophysiology and clinical characteristics of pain in most common locations in cancer patients. J. Physiology and Pharmacology. 2016; 67(6):787-799.
Кит О.И., Франциянц Е.М., Котиева И.М. и др. Динамика тканевой системы регуляторов плазминогена при меланоме кожи на фоне хронической боли у самок мышей. Трансляционная медицина. 2018,5(2):38-46. DOI: 10.18705/2311-4495-2018-5-2-38-46
Франциянц Е.М., Кит О.И., Котиева И.М. и др. Тканевая система регуляции плазминогена в динамике меланомы кожи у мышей-самцов, воспроизведенной на фоне хронической боли. Известия вузов Северо-Кавказского региона. Естественные науки. 2019; 199(1): 112-121.
Hald A, eickhardt H, Maerkedahl RB, Feldborg CW, egerod KL, engelholm LH, Laerum oD, Lund LR, R0n0 B. Plasmin-driven fibrinolysis facilitates skin tumor growth in a gender-dependent manner. FAsEB J. 2012; 26(11): 4445-57. DOI: 10.1096/fj.12-208025
R0n0 Birgitte, Lars Henning engelholm, Leif R0ge Lund, Andreas Hald. Gender Affects skin Wound Healing in Plasminogen Deficient Mice. PLos one. 2013; 8(3): e59942. 10.1371 / journal.pone.0059942. DOI: 10.1371/journal.pone.0059942
Mazzieri R., Pietrogrande G., Gerasi L. et al. Urokinase Receptor Promotes skin tumor Formation by Preventing epithelial Cell Activation of Notch1. Cancer Res. 2015; 75(22): 4895-909. DOI: 10.1158/0008-5472.CAN-15-0378
Yamanaka H., obata K., Fukuoka т. et al. Induction of plasminogen activator inhibitor-1 and -2 in dorsal root ganglion neurons after peripheral nerve injury, neuroscience. 2005, 132:183-91.
Yamanaka H., Kobayashi K., okubo M. et al. Annexin A2 in primary afferents contributes to neuropathic pain associated with tissue type plasminogen activator. Neuroscience. 2016, 314: 189-99. DOI: 10.1016/j.neurosci-ence.2015.11.058
Кит О.И., Франциянц Е.М., Котиева И.М. и др. Некоторые механизмы повышения злокачественности меланомы на фоне хронической боли у самок мышей. Российский журнал боли. 2017;2(53):14-20.
Wu F., Catano M., Echeverry R. et al. Urokinase-type plasminogen activator promotes dendritic spine recovery and improves neurological outcome following ischemic stroke. J. Neurosci. 2014; 34: 14219-32. doi: 10,1523 / JNEURoSCI.5309-13.2014.
Schuliga M. The inflammatory actions of coagulant and fibrinolytic proteases in disease. Mediators Inflamm. 2015; 2015: 4376-95. DOI: 10.1155/2015/437695
Сидоренко Ю.С., Мусиенко Н.В., Франциянц Е.М. Некоторые показатели активности протеолитической системы в ткани злокачественной опухоли и перифокальной зоны при различных локализациях рака. Вестник Южного научного центра рАН. 2008; 4(2): 93-8.
McMahon B.J., Kwaan H.C. Components of the Plasminogen-Plasmin System as Biologic Markers for Cancer. Adv Exp Med Biol. 2015; 867: 145-56. DOI: 10.1007/978-94-017-7215-0_10
Mahmood N., Mihalcioiu C., Rabbani S.A. Multifaceted Role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): Diagnostic, Prognostic, and Therapeutic Applications. Front oncol. 2018; 8: 24. DOI: 10.3389/fonc.2018.00024
Merino P., Diaz A., Jeanneret V. et al. Urokinase-type Plasminogen Activator (uPA) Binding to the uPA Receptor (uPAR) Promotes Axonal Regeneration in the Central Nervous System. J Biol Chem. 2017; 292(7): 2741-53. DOI: 10.1074/jbc.M116.761650
Sukocheva o.A., Li B., Due S.L. et al. Androgens and esophageal cancer: What do we know? World. J. Gastroenterol. 2015; 21(20): 6146-6156.
Pavon M.A., Arroyo-Solera I., Virtudes Cespedes M. et al. uPA/uPAR and SERPINE1 in head and neck cancer: role in tumor resistance, metastasis, prognosis and therapy. Oncotarget. 2016; 35(7): 57351-57366. DOI: 10.18632/oncotarget.10344
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