Choong Peter F M, Nadesapillai Anne P W
Department of Orthopaedics, The University of Melbourne, Melbourne, Australia.
Clin Orthop Relat Res. 2003 Oct(415 Suppl):S46-58. doi: 10.1097/01.blo.0000093845.72468.bd.
The urokinase plasminogen activator (uPA) system is central to a spectrum of biologic processes including fibrinoloysis, inflammation, atherosclerotic plaque formation, matrix remodeling during wound healing, tumor invasion, angiogenesis, and metastasis. Binding of uPA with its receptor (uPAR) initiates a proteolytic cascade that results in the conversion of plasminogen to plasmin. Plasmin through its own proteolytic function degrades a range of extracellular basement membrane components and activates others such as the metalloproteinases. Independent of catalytic activity, uPAR also is involved in cell signaling, interactions with integrins, cell motility, adhesion and invasion, and angiogenesis. Over expression of uPA or uPAR is a feature of malignancy and is correlated with tumor progression and metastasis. In contrast, inhibition of expression of these components leads to a reduction in the invasive and metastatic capacity of many tumors. Strategies that target uPA or its receptor with the aim of disrupting the interaction between the two or the ligand independent actions of uPAR include antisense technology, monoclonal antibodies, cytotoxic antibiotics, and synthetic inhibitors of uPA. Targeted therapy is a goal of future cancer treatment and the uPA system is a likely candidate for manipulation.
尿激酶型纤溶酶原激活物（uPA）系统在一系列生物过程中起核心作用，这些过程包括纤维蛋白溶解、炎症、动脉粥样硬化斑块形成、伤口愈合过程中的基质重塑、肿瘤侵袭、血管生成和转移。uPA与其受体（uPAR）结合引发蛋白水解级联反应，导致纤溶酶原转化为纤溶酶。纤溶酶通过自身的蛋白水解功能降解一系列细胞外基底膜成分，并激活其他成分，如金属蛋白酶。独立于催化活性之外，uPAR还参与细胞信号传导、与整合素的相互作用、细胞运动、黏附和侵袭以及血管生成。uPA或uPAR的过度表达是恶性肿瘤的一个特征，并且与肿瘤进展和转移相关。相反，抑制这些成分的表达会导致许多肿瘤的侵袭和转移能力降低。以破坏两者之间的相互作用或uPAR的配体非依赖性作用为目标靶向uPA或其受体的策略包括反义技术、单克隆抗体、细胞毒性抗生素和uPA的合成抑制剂。靶向治疗是未来癌症治疗的目标，uPA系统很可能是可供操控的对象。
