title: Coordinate expression of urinary-type plasminogen activator and its receptor accompanies malignant transformation of the ovarian surface epithelium.
abstract: OBJECTIVE
  Because elevated expression and cell surface association of urinary-type plasminogen activator have been linked to invasive potential in certain tumor types, we examined the expression of urinary-type plasminogen activator and urinary-type plasminogen activator receptor in ovarian epithelial carcinoma tissues and cells as compared with normal ovarian epithelium.
  
  
  METHODS
  Monoclonal antibodies specific for urinary-type plasminogen activator and urinary-type plasminogen activator receptor were used for immunohistochemical staining of tissues and cells to assess expression of these antigens in frozen sections of normal and tumor tissue. Substrate zymography was used to detect plasminogen activator activity in ovarian carcinoma ascites and in conditioned media of cultured cells, whereas a Western blot assay was used to identify urinary-type plasminogen activator receptor in cultured cells.
  
  
  RESULTS
  Normal ovarian epithelium expressed urinary-type plasminogen activator receptor (4/4 positive) but little or no urinary-type plasminogen activator (0/4 positive), whereas epithelial ovarian carcinomas frequently expressed urinary-type plasminogen activator (4/8 positive) in conjunction with urinary-type plasminogen activator receptor (7/9 positive). High levels of urinary-type plasminogen activator were detected in 15 of 19 samples of ascites. DOV 13, OVCA 420, OVCA 429, OVCA 432, and OVCA 433 cell lines secreted urinary-type plasminogen activator in variable quantities, whereas normal ovarian epithelial cells did not secrete any detectable plasminogen activator. Urinary-type plasminogen activator receptor had similar levels of expression in all cancer cell lines and normal ovarian epithelium.
  
  
  CONCLUSIONS
  Overexpression of urinary-type plasminogen activator is associated with malignant transformation of the ovarian epithelium. Increased cell surface proteolysis mediated by urinary-type plasminogen activator bound to cell surface urinary-type plasminogen activator receptor may contribute to metastatic behavior in ovarian carcinoma.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710.
authors.forename: T N
authors.initials: TN
authors.lastname: Young
authors.forename: G C
authors.initials: GC
authors.lastname: Rodriguez
authors.forename: T L
authors.initials: TL
authors.lastname: Moser
authors.forename: R C
authors.initials: RC
authors.lastname: Bast
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
authors.forename: M S
authors.initials: MS
authors.lastname: Stack
mesh_terms: D002277:Carcinoma / Q000737:chemistry* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000378:metabolism; D010053:Ovary / Q000737:chemistry* / Q000378:metabolism; D010960:Plasminogen Activators / Q000032:analysis*; D011956:Receptors, Cell Surface / Q000032:analysis*; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000378:metabolism
chemical_list: C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator