Changes in the content of some components of the plasminogen activation system in the plasma of bladder cancer patients

V. Dmytryk, O. Savchuk, P. Yakovlev
Taras Shevchenko National University of Kyiv, Kyiv; Taras Shevchenko National University of Kyiv, Kyiv; O. Bogomolets National Medical University, Kyiv

Abstract


Bladder cancer (BC) continues to be a disease with a high mortality rate. Bladder cancer is the sixth for men and seventeenth for women in the
incidence of malignancy worldwide. The invasion and metastasis of malignant tumors are caused by a sequence of processes, including loss of cell-cell and / or cell-matrix adhesion, proteolysis, and induction of angiogenesis. Different protease systems are involved in these processes, especially during the invasion and development of metastases. One such protease system is a plasminogen activation system or fibrinolysis system. Changes in the balance of plasminogen activation systems have been investigated in many types of malignancies, and these changes may not only indicate the functioning of this system but may also have prognostic significance. In malignancies, the components of this system are involved in the growth, invasion, and metastasis of tumors, affecting cell migration and angiogenesis. The main, but a well-studied component of the plasminogen activation system is serine proteinase – urokinase-type plasminogen activator (uPA). In contrast to uPA, tissue-type plasminogen activator (tPA) is characterized by a high affinity for fibrin and is involved in thrombolysis. Both types of plasminogen activators are synthesized in tumor tissues: tPA and uPA. The largest player among the inhibitors of fibrinolysis is the plasminogen activator inhibitor type 1 (PAI-1), involved in the pathogenesis of many cardiovascular diseases, as well as in cancer. The purpose of this study was to detect changes in the content of plasminogen activator tissue type tPA and PAI-1 in the blood plasma of patients with BC at different stages of the disease. The study involved 40 men who were verified with a diagnosis of BC. The content of tPA and PAI-1 in preoperative blood plasma was determined by enzyme immunoassay in ELISA modification. In our study, changes in the tPA and PAI-1 content of the blood plasma at different stages were identified, which can characterize tumor growth and invasion and can supplement existing disease information.

Keywords


bladder cancer, tPA, PAI-1, plasminogenactivation system

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References


Bachmann F, Kruithof IE: Tissue plasminogen activator: chemical and physiological aspects. Semin Thromb Hemost 1984; 10: 6–17.

Bajou K. Absence of host plasminogen activator inhibitor 1 prevents cancerinvasion andvascularization / K. Bajou, A. Noel, R. D. Gerard et al. // NatMed. – 1998 – Vol. 4. – P. 923–928.

Becker M, Tilki D, Szarvas T, Rubben H, Ergun S. Urinebased markers of angiogenesis in bladder cancer. Urologe A. 2009; 48:609-614.

Blasi F, Riccio A, Sebastio G: Human plasminogen activators. Genes and proteins structure. Horiz Biochem Biophys 1986; 8: 377–414.

Collen D, Lijnen HR: Tissue-type plasminogen activator: a historical perspective and personal account. J Thromb Haemost 2004; 2: 541–546.

Dellas C, D.J. Loskutoff, Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease, Thromb. Haemost. 93 (2005) 631–640.

Geis T., C. Döring, R. Popp, N. Grossmann, I. Fleming, M.L. Hansmann, N. Dehne, et al. HIF-2alpha-dependent PAI-1 induction contributes to angiogenesis in hepatocellular carcinoma, Exp. Cell. Res. 331 (2015) 46–57.

Gontero P, Banisadr S, Frea B, Brausi M. Metastasis markers in bladder cancer: a review of the literature and clinical considerations. Eur Urol. 2004; 46:296-311.

Herszényi L., M. Plebani, R. Cardin, P. Carraro, P.M. De, G. Roveroni, R. Naccarato, F. Farinati, The role of urokinase-type plasminogen activator and its inhibitor PAI-1 in gastric cancer, Acta Physiol. Hung. 83 (1995) 213–221.

Ishchuk T. Plasma levels of MMPs and TIMP-1 in urinary bladder cancer patients / T.V. Ishchuk, D. Glavachek, O.M. Savchuk et al. // Biomedical Research and Therapy, 2018. – №5. – С. 1931–1940.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: a cancer journal for clinicians. 2011;61:69–90.

Li S, Wei X, He J, Tian X, Yuan S, Sun L. Plasminogen activator inhibitor-1 in cancer research. Biomed Pharmacother. 2018; 105:83–94.

McMahon B, Kwaan HC. The plasminogen activator system and cancer. Pathophysiol Haemost Thromb. 2008;36(3-4):184–194.

Mio H., O. Mitsuhiko, K. Yusuke, S. Yui, Y. Yusuke, K. Nobuyoshi, T. Fumitaka, F. Tomohiro, K. Akira, I. Hisao, PAI‐1, a target gene of miR‐143, regulates invasion and metastasis by upregulatingMMP‐13 expression of human osteosarcoma, Cancer Med. 5 (2016) 892–902.

Palmieri D. Plasminogenactivator inhibitor-1 and -3 increase cell adhesion andmotility of MDA-MB-435 B breast cancer cells / D. Palmieri, J. W. Lee,R. L. Juliano,F. C. Church // J Biol Chem. – 2002. – Vol. 277. – P. 40950–40957.

Palmirotta R., P. Ferroni, A. Savonarola, F. Martini, F. Ciatti, A. Laudisi, V. Sini, G.D. Monte, F. Guadagni, M. Roselli, Prognostic value of pre-surgical plasma PAI-1 (plasminogen activator inhibitor-1) levels in breast cancer, Thromb. Res. 124 (2009) 403.

Rijken DC. Plasminogen activators and plasminogen activator inhibitors: biochemical aspects. Baillieres Clin Haematol. 1995;8:291-312.

Satsuki M., K. Kazuyuki, T. Masafumi, I. Atsuhiko, D. Takashi, U. Toshinori, I. Masumi, S. Shogo, N. Satoru, M. Toshio, Inhibition of plasminogen activator inhibitor-1 is a potential therapeutic strategy in ovarian cancer, Cancer Biol. Ther. 16 (2015) 253–260.

Stahl A. Melanoma cell migration on vitronectin: regulation bycomponents of the plasminogen activationsystem / A. Stahl, B. M. Mueller //Int J Cancer. – 1997. – Vol. 71. – P. 116–122.

Trousseau A: Phlegmasia alba dolens; in Trousseau A (ed): Clinique médicinale de

Zhu CZ, Ting HN, Ng KH, Ong TA. A review on the accuracy of bladder cancer detection methods. J Cancer. 2019;10(17):4038–4044.

Received: 16.01.2020

Revised: 17.02.2020

Signed for the press: 17.02.2020




DOI: http://dx.doi.org/10.17721/1728_2748.2020.80.15-19

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