title: The urokinase-type plasminogen activator (uPA) system as a biomarker and therapeutic target in human malignancies.
abstract: BACKGROUND
  The urokinase plasminogen activator (uPA) system, comprising the serine protease uPA, its cognate receptor, uPAR, and two endogenous inhibitors, plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2), is a key player in the break-down of extracellular matrix (ECM) and basement membrane. Elevated expression of uPA and uPAR is observed in numerous cancer types and associated with poor prognosis.
  
  
  METHODS
  In addition to the aberrant expression during tumor development, the components of uPA system are functionally involved in various processes that are prerequisite for cancer progression. These processes include, but not limited to, ECM degradation, angiogenesis, cell proliferation, adhesion, migration and epithelial-mesenchymal transition. All of these findings implicate uPA system as a target for cancer treatment. Thus, therapeutic agents and approaches to targeting the constituents of uPA system, mainly at their expression level and biological activities, have been extensively used in antineoplastic investigations.
  
  
  CONCLUSIONS
  Because of promising results obtained from previous preclinical studies, several clinical trials aimed at inhibiting the expression or function of uPA/uPAR have been completed or are ongoing. In these trials, favorable outcomes in reducing metastatic spread and extending the lifespan of cancer patients have been reported, and no severe adverse events were observed.
authors.affiliation: a Whole-Genome Research Core Laboratory of Human Diseases , Chang Gung Memorial Hospital , Keelung , Taiwan.|b Department of Dermatology, Drug Hypersensitivity Clinical and Research Center , Chang Gung Memorial Hospital , Linkou , Taiwan.
authors.forename: Shih-Chi
authors.initials: SC
authors.lastname: Su
authors.affiliation: c Institute of Oral Sciences , Chung Shan Medical University , Taichung , Taiwan.|d Department of Dentistry , Chung Shan Medical University Hospital , Taichung , Taiwan.
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: e Institute of Medicine , Chung Shan Medical University , Taichung , Taiwan.
authors.forename: Wei-En
authors.initials: WE
authors.lastname: Yang
authors.affiliation: a Whole-Genome Research Core Laboratory of Human Diseases , Chang Gung Memorial Hospital , Keelung , Taiwan.
authors.forename: Wen-Lang
authors.initials: WL
authors.lastname: Fan
authors.affiliation: e Institute of Medicine , Chung Shan Medical University , Taichung , Taiwan.|f Department of Medical Research , Chung Shan Medical University Hospital , Taichung , Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D014568:Urokinase-Type Plasminogen Activator
keywords: Angiogenesis; extracellular matrix (ECM); integrin; malignancy; matrix metalloprotease (MMP); metastasis; urokinase plasminogen activator (uPA)