Cancer Research Laboratories, University of New South Wales, Sydney, NSW, Australia.
Future Oncol. 2009 Nov;5(9):1487-99. doi: 10.2217/fon.09.108.
Proteolysis of extracellular matrix (ECM) and basement membrane is an essential mechanism used by cancer cells for their invasion and metastasis. The ECM proteinases are divided into three groups: metalloproteinases, cysteine proteinases and serine proteinases. The urokinase plasminogen activator (uPA) system is one of the serine proteinase systems involved in ECM degradation. Members of this system, including uPA and its receptor (uPAR), are overexpressed in several malignant tumors. This system plays a major role in adhesion, migration, invasion and metastasis of cancer cells, thus making it an important target for anticancer drug therapy. Several strategies, including the use of antisense oligodeoxynucleotides, ribozymes, DNAzyme, RNAi, uPA inhibitors, soluble uPAR, catalytically inactive uPA fragments, synthetic peptides and synthetic hybrids are under study, as they interfere with the expression and/or activity of uPA or uPAR in tumor cells. Herein, we discuss the various pharmaceutical strategies under investigation to combat the uPA activity in cancer.
细胞外基质（ECM）和基底膜的蛋白水解是癌细胞侵袭和转移所必需的机制。ECM 蛋白酶分为三类：金属蛋白酶、半胱氨酸蛋白酶和丝氨酸蛋白酶。尿激酶纤溶酶原激活物（uPA）系统是参与 ECM 降解的丝氨酸蛋白酶系统之一。该系统的成员，包括 uPA 和其受体（uPAR），在几种恶性肿瘤中过度表达。该系统在癌细胞的黏附、迁移、侵袭和转移中起主要作用，因此成为抗癌药物治疗的重要靶点。目前正在研究几种策略，包括使用反义寡核苷酸、核酶、DNA 酶、RNAi、uPA 抑制剂、可溶性 uPAR、无催化活性的 uPA 片段、合成肽和合成杂合体，因为它们可以干扰肿瘤细胞中 uPA 或 uPAR 的表达和/或活性。在此，我们讨论了正在研究的各种药物策略，以对抗癌症中的 uPA 活性。
