Urokinase plasminogen activator system as a potential target for cancer therapy. 2009

Ahmed H Mekkawy, and David L Morris, and Mohammad H Pourgholami
Cancer Research Laboratories, University of New South Wales, Sydney, NSW, Australia.

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.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D014568 Urokinase-Type Plasminogen Activator A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES. Plasminogen Activator, Urokinase-Type,U-Plasminogen Activator,Urinary Plasminogen Activator,Urokinase,Abbokinase,Kidney Plasminogen Activator,Renokinase,Single-Chain Urokinase-Type Plasminogen Activator,U-PA,Single Chain Urokinase Type Plasminogen Activator,U Plasminogen Activator,Urokinase Type Plasminogen Activator
D055293 Receptors, Urokinase Plasminogen Activator An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN. Antigens, CD87,Urokinase Plasminogen Activator Receptor,Urokinase Type Plasminogen Activator Receptor,Urokinase-Type Plasminogen Activator Receptor,CD87 Antigen,Plasminogen Activator Receptor, Urokinase Type,Plasminogen Activator, Urokinase Receptor,Plasminogen Activator, Urokinase Receptors,Receptor, Pro-Urokinase,Receptor, Urokinase Plasminogen Activator,U-PA Receptor,Upar Receptor,Urokinase Plasminogen Activator Receptors,Urokinase-Type Plasminogen Activator Receptors,Antigen, CD87,CD87 Antigens,Pro-Urokinase Receptor,Receptor, Pro Urokinase,Receptor, U-PA,Receptor, Upar,U PA Receptor,Urokinase Type Plasminogen Activator Receptors

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