title: Differential gene expression of urokinase-type plasminogen activator and its receptor in human renal cell carcinoma.
abstract: The urokinase-type plasminogen activator (uPA) system plays a central role in extracellular matrix degradation, cell migration, and invasion. uPA belongs to the family of serine proteases. It has been shown that its proteolytic activity is involved in the metastatic process by activation and binding to its receptor (uPAR). Previous studies in several organ systems have elucidated a higher uPA expression in malignant tissue in comparison to normal tissue. In this study uPA and uPAR gene expression were investigated in 18 human renal cell carcinoma (RCC) specimens in comparison with adjacent non-malignant renal tissues. mRNA in situ hybridisation and immunohistochemical staining were performed. mRNA of uPA and uPAR was significantly higher expressed in 56% (10/18) and 72% (13/18) of the RCC specimens in comparison to the adjacent non-malignant renal tissue (p<0.0001), respectively. uPA-mRNA and uPAR-mRNA were expressed predominantly in malignant renal cells and in very few surrounding stromal cells. The elevated expression of uPAR-protein in RCC reached statistical significance compared to adjacent normal tissue (p=0.007). uPAR genes were higher expressed in comparison to uPA alone. There was a statistical trend that higher expression of uPA and uPAR corresponded with TNM tumour stage and grade in RCC. Further investigations need to be done with larger sample sizes to prove a correlation of expression between uPA and uPAR to a more aggressive phenotype. We conclude that uPA- and uPAR are overexpressed in RCC and could function as tumour markers.
authors.affiliation: Department of Urology, University Hospital Charité, Humboldt University Berlin, D-10098 Berlin, Germany.
authors.forename: Venugopal
authors.initials: V
authors.lastname: Bhuvarahamurthy
authors.forename: Joerg
authors.initials: J
authors.lastname: Schroeder
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Jan
authors.initials: J
authors.lastname: Roigas
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Manfred
authors.initials: M
authors.lastname: Johannsen
authors.forename: Michael
authors.initials: M
authors.lastname: Lein
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Loening
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schnorr
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
authors.forename: Andrea
authors.initials: A
authors.lastname: Staack
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator