title: Increased expression of urokinase plasminogen activator and its cognate receptor in human seminomas.
abstract: BACKGROUND
  The urokinase plasminogen activating system (uPAS) is implicated in neoplastic progression and high tissue levels of uPAS components correlate with a poor prognosis in different human cancers. Despite that, relative few studies are available on the expression and function of the uPAS components in human seminomas. In the present study we characterized the expression of the urokinase plasminogen activator (uPA), its cognate receptor (uPAR) and the uPA inhibitors PAI-1 and PAI-2 in normal human testis and seminomas.
  
  
  METHODS
  The expression of the above genes was evaluated by means of quantitative RT-PCR, western blot, zymographic analysis and immunohistochemistry.
  
  
  RESULTS
  Quantitative RT-PCR analysis of 14 seminomas demonstrated that uPA and uPAR mRNAs were, with respect to control tissues, increased in tumor tissues by 3.80 +/- 0.74 (p < 0.01) and 6.25 +/- 1.18 (p < 0.01) fold, respectively. On the other hand, PAI-1 mRNA level was unchanged (1.02 +/- 0.24 fold), while that of PAI-2 was significantly reduced to 0.34 +/- 0.18 (p < 0.01) fold. Western blot experiments performed with protein extracts of three seminomas and normal tissues from the same patients showed that uPA protein levels were low or undetectable in normal tissues and induced in tumor tissues. On the same samples, zymographic analysis demonstrated increased uPA activity in tumor tissue extracts. Western blot experiments showed that also the uPAR protein was increased in tumor tissues by 1.83 +/- 0.15 fold (p < 0.01). The increased expression of uPA and uPAR was further confirmed by immunohistochemical staining performed in 10 seminomas and autologous uninvolved peritumoral tissues. Finally, variation in the mRNA level of PAI-1 significantly correlated with tumor size.
  
  
  CONCLUSIONS
  We demonstrated the increased expression of uPA and uPAR in human seminomas with respect to normal testis tissues, which may be relevant in testicular cancer progression.
authors.affiliation: Department of Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ulisse
authors.forename: Enke
authors.initials: E
authors.lastname: Baldini
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Steno
authors.initials: S
authors.lastname: Sentinelli
authors.forename: Patrizia
authors.initials: P
authors.lastname: Gargiulo
authors.forename: Brancato
authors.initials: B
authors.lastname: Valentina
authors.forename: Salvatore
authors.initials: S
authors.lastname: Sorrenti
authors.forename: Anna
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: Enrico
authors.initials: E
authors.lastname: De Antoni
authors.forename: Massimino
authors.initials: M
authors.lastname: D'Armiento
mesh_terms: D000328:Adult; D015153:Blotting, Western; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007558:Italy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018239:Seminoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D013736:Testicular Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis* / Q000235:genetics; D055815:Young Adult
chemical_list: C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D055293:Receptors, Urokinase Plasminogen Activator; C051321:SERPINE1 protein, human; D014568:Urokinase-Type Plasminogen Activator
references.citation: Bull Assoc Anat (Nancy). 1991 Mar;75(228):123-6
references.pmid: 1782448
references.citation: Cancer Res. 2005 Jul 1;65(13):5588-98
references.pmid: 15994931
references.citation: Med Res Rev. 2004 Jan;24(1):13-39
references.pmid: 14595671
references.citation: Rev Reprod. 1999 May;4(2):90-100
references.pmid: 10357096
references.citation: J Urol. 1997 May;157(5):1705-9; discussion 1709-10
references.pmid: 9112510
references.citation: Clin Chem. 2002 Aug;48(8):1194-7
references.pmid: 12142372
references.citation: Am J Surg Pathol. 1993 Nov;17(11):1075-91
references.pmid: 8214253
references.citation: Int J Cancer. 1997 Jul 3;72(1):1-22
references.pmid: 9212216
references.citation: J Natl Cancer Inst. 2002 Jan 16;94(2):116-28
references.pmid: 11792750
references.citation: J Biol Chem. 1991 Nov 5;266(31):20960-4
references.pmid: 1939146
references.citation: Breast Cancer Res. 2004;6(3):109-18
references.pmid: 15084231
references.citation: Nat Rev Mol Cell Biol. 2002 Dec;3(12):932-43
references.pmid: 12461559
references.citation: Nat Rev Cancer. 2008 Jul;8(7):535-45
references.pmid: 18548086
references.citation: FEBS J. 2005 Oct;272(19):4858-67
references.pmid: 16176260
references.citation: JAMA. 1965 Sep 13;193:960-2
references.pmid: 14341150
references.citation: Int J Cancer. 2002 Aug 10;100(5):501-6
references.pmid: 12124797
references.citation: Int J Oncol. 2003 Dec;23(6):1615-35
references.pmid: 14612934
references.citation: Thromb Haemost. 1997 Jul;78(1):285-96
references.pmid: 9198168
references.citation: J Urol. 1999 Jan;161(1):342-8
references.pmid: 10037435
references.citation: Anal Biochem. 1976 May 7;72:248-54
references.pmid: 942051
references.citation: Thromb Haemost. 1993 Dec 20;70(6):989-94
references.pmid: 8165623
references.citation: Clin Orthop Relat Res. 2003 Oct;(415 Suppl):S46-58
references.pmid: 14600592
references.citation: Curr Cancer Drug Targets. 2009 Feb;9(1):32-71
references.pmid: 19200050
references.citation: J Pathol. 2008 Feb;214(3):283-93
references.pmid: 18095256
references.citation: J Natl Cancer Inst. 1996 Jun 5;88(11):727-33
references.pmid: 8637026
references.citation: Clin Biochem. 2004 Jul;37(7):541-8
references.pmid: 15234235
references.citation: Histopathology. 1978 May;2(3):157-70
references.pmid: 27442
references.citation: Curr Pharm Des. 2004;10(1):39-49
references.pmid: 14754404
references.citation: Blood. 1987 Feb;69(2):381-7
references.pmid: 3099859
references.citation: Endocrinology. 1998 Feb;139(2):741-7
references.pmid: 9449648
references.citation: Circ Res. 2003 May 2;92(8):827-39
references.pmid: 12730128
references.citation: Int J Dev Biol. 2004;48(5-6):545-57
references.pmid: 15349829
references.citation: Arterioscler Thromb Vasc Biol. 2001 Jul;21(7):1104-17
references.pmid: 11451738
references.citation: Cell. 2000 Jan 7;100(1):57-70
references.pmid: 10647931
references.citation: Trends Biotechnol. 2007 Jan;25(1):33-9
references.pmid: 17084931
references.citation: J Biol Chem. 1995 Nov 17;270(46):27894-904
references.pmid: 7499264
references.citation: Virchows Arch. 2005 Sep;447(3):610-25
references.pmid: 15968545
references.citation: Semin Cancer Biol. 2000 Dec;10(6):415-33
references.pmid: 11170864
references.citation: Anal Biochem. 1987 Apr;162(1):156-9
references.pmid: 2440339