Division of Molecular Biology, Department of Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia.
Thromb Haemost. 2018 Dec;118(12):2020-2036. doi: 10.1055/s-0038-1675399. Epub 2018 Nov 12.
Urokinase plasminogen activator (uPA) system regulates extracellular matrix remodelling by activating ubiquitous protease plasmin in many important physiological processes. The system components include uPA, plasminogen activator inhibitors (PAIs) and uPA receptor (uPAR). Besides its role in physiological processes, uPA system is active in most tumour types where its aberrant regulation has been associated with the development of metastatic phenotype. In vitro and in vivo studies have shown that the over-expression of uPA, PAI-1 and uPAR not only enhances tumour cell invasion capacity and metastasis, but also corresponds to a higher risk of disease correlating with traditional clinicopathological features which makes them potential prognostic biomarkers and therapeutic targets in a wide range of human malignancies. This review focuses on uPA system's prognostic and predictive role in several types of human cancers, summarizing its activities in cancer development and highlighting the importance of addressing all unanswered questions before bridging the gap between laboratory findings to clinic use of uPA system's components as cancer biomarkers.
尿激酶型纤溶酶原激活物（uPA）系统通过激活广泛存在的蛋白酶纤溶酶来调节细胞外基质的重塑，在许多重要的生理过程中发挥作用。该系统的组成部分包括 uPA、纤溶酶原激活物抑制剂（PAIs）和 uPA 受体（uPAR）。除了在生理过程中的作用外，uPA 系统在大多数肿瘤类型中都很活跃，其异常调节与转移性表型的发展有关。体外和体内研究表明，uPA、PAI-1 和 uPAR 的过度表达不仅增强了肿瘤细胞的侵袭能力和转移能力，而且与传统的临床病理特征相关的疾病风险更高，这使得它们成为广泛的人类恶性肿瘤中潜在的预后生物标志物和治疗靶点。本综述重点关注 uPA 系统在几种人类癌症中的预后和预测作用，总结其在癌症发展中的作用，并强调在将实验室发现与临床应用 uPA 系统成分作为癌症生物标志物联系起来之前，解决所有未解答问题的重要性。
