title: Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinases are associated with serous epithelial ovarian cancer progression.
abstract: OBJECTIVE
  Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloproteinases (MMP-2 and MMP-9), and of the serine protease urokinase-type plasminogen activator (uPA) in serous epithelial carcinoma of the ovary were investigated.
  
  
  METHODS
  Plasminogen antigen was analyzed in tissue extracts and in the urine of patients with normal (n = 12), benign (n = 6), borderline (n = 9), and invasive serous tumors (n = 22) by Western immunoblotting using rabbit polyclonal plasminogen and murine monoclonal angiostatin antibodies. In the same tissue extracts, semiquantitative estimates of MMP-2, MMP-9, total MMP activity, and uPA activity were determined using semiquantitative gelatin zymography in the presence or absence of human plasminogen.
  
  
  RESULTS
  Bands corresponding to Glu-plasminogen (approximately 92 kDa) and Lys-plasminogen (approximately 86 kDa) were detected in all ovarian tissues and in corresponding urine samples. Densitometric analysis of combined Glu- or Lys-plasminogen levels showed significantly decreased levels in malignant compared to normal tissue. In Grade 3 cancers, there was no evidence of Glu-plasminogen or angiostatin. MMP activity was significantly elevated in both borderline and in Grade 3 ovarian cancer tissues. Increased tissue uPA activity on zymograms was detected only in Grade 3 ovarian cancer tissue.
  
  
  CONCLUSIONS
  These data suggest that proteolytic activity of the plasminogen activation cascade increases in serous epithelial ovarian carcinoma.
authors.affiliation: Department of Obstetrics and Gynaecology, The Royal Women's Hospital, University of Melbourne, Victoria Parkville 3053, Australia. padma@unimelb.edu.au
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
authors.forename: Gillian
authors.initials: G
authors.lastname: Barker
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Nowell
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Rice
authors.forename: Mark S
authors.initials: MS
authors.lastname: Baker
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quinn
mesh_terms: D015153:Blotting, Western; D018284:Cystadenocarcinoma, Serous / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D010958:Plasminogen / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9