Urokinase plasminogen activator system as a potential target for cancer therapy

Abstract

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.