Plasminogen Activator System and its Clinical Significance in Patients with a Malignant Disease

Česká verzia

Authors: J. Halámková ¹; I. Kiss ¹; J. Tomášek ¹; Z. Pavlovský ²; Z. Čech ³; Š. Tuček ¹; L. Hanáková ⁴; M. Moulis ²; M. Penka ³
Authors place of work: Klinika komplexní onkologické péče, Masarykův onkologický ústav a LF MU Brno ¹; Patologicko-anatomický ústav FN Brno a LF MU ²; Oddělení klinické hematologie FN Brno a LF MU ³; Interní hematoonkologická klinika FN Brno a LF MU ⁴
Published in the journal: Klin Onkol 2011; 24(6): 418-423
Category: Reviews

Summary

Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, a serine protease participating in the activation of matrixmetaloproteinases, latent elastases, growth factors and cytokines involved in the degradation of extracellular matrix elements. Together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI-1, PAI-2, PAI-3 and protease nexin), it forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. Plasminogen activator inhibitor 1 inhibits uPA-dependent invasiveness of some cancer cell lines. The vitronectin-PAI-1 complex inhibits migration of smooth muscle cells by binding α_vβ₃ integrin to vitronectin. PAI-1 or its deficiency interferes with signalling pathways such as PI3K/Akt and JAK/STAT and it is included in the processes of maintaining the integrity of the endothelial cells and thereby regulation of cell death. PAI-1 affects apoptosis by reducing cell adhesion and functioning of intracellular signalling pathways. The individual components of PAS undoubtedly play an important role in angiogenesis and metastasising of malignant tumours. In the near future, results of published studies with various types of cancer could be reflected in diagnostic and therapeutic algorithms and, at the same time, could serve as the goal for targeted therapies.

Key words:
plasminogen activators – U-PA – U-PA receptor – PAI-1 – PAI-2

This study was supported by the following research programme of the Ministry of Health of the Czech Republic: FUNDIN MO0MOU2005.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
3. 4. 2011

Accepted:
20. 9. 2011

Zdroje

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