Targeting urokinase-type plasminogen activator and its receptor for cancer therapy.
Cancer invasion and metastasis are highly complex processes and a serine protease urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been postulated to play a central role in the mediation of cancer progression. Of note, malignant tumor urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor levels have been found to vary considerably, and to be related to patient prognosis. In mouse models, the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been studied extensively as a target for anticancer therapy using a variety of approaches. In this review, we discuss the advances in the various modalities that have been used to target the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system, including protein-based and peptide-based drugs, antisense therapy, and RNA interference technology. In particular, preclinical mouse model studies that used human tumor xenografts are reviewed.
Nozaki
Shinichi
S
Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Japan. snozaki@med.kanazawa-u.ac.jp
Endo
Yoshio
Y
Nakahara
Hirokazu
H
Yoshizawa
Kunio
K
Ohara
Teruhisa
T
Yamamoto
Etsuhide
E
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016375:Antisense Elements (Genetics) / Q000627:therapeutic use; D016503:Drug Delivery Systems; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000628:therapy*; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics*
D000970:Antineoplastic Agents; D016375:Antisense Elements (Genetics); C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator