title: Osteopontin induces soluble urokinase-type plasminogen activator receptor production and release.
abstract: BACKGROUND
  Osteopontin (OPN) and soluble urokinase plasminogen activator receptor (suPAR) have been proposed as markers of disease severity and risk-stratification in infection and inflammation. In breast cancer, OPN and the membrane bound form of urokinase plasminogen activator receptor (uPAR) are functionally related, as OPN-induced cell migration depends on uPAR triggering by urokinase plasminogen activator (uPA). The aim of this study was to prospectively evaluate the kinetic of OPN and suPAR blood levels in patients developing septic shock (SS) compared to those not developing SS, and to investigate the relationships between these two biomarkers in immune cells in vitro.
  
  
  METHODS
  We measured the levels of OPN and suPAR for 15 days in forty-three patients, defined a priory as at risk to develop septic shock. Moreover, we investigated in vitro the effect of recombinant OPN on uPAR and suPAR expression in monocytes.
  
  
  RESULTS
  We found that OPN and suPAR levels were directly correlated to each other both at intensive care unit admission and on the day patients met SIRS/sepsis or septic shock criteria. In patients developing septic shock, OPN increased prior to suPAR and was already detectable up to 4 days before the shock development. In vitro, OPN induced suPAR production in monocytes by increasing both uPAR gene expression, and suPAR release from the cell surface.
  
  
  CONCLUSIONS
  These data suggest that OPN is partly responsible for the increased plasma levels of suPAR and might be a valuable tool to predict the occurrence of septic shock.
authors.affiliation: Azienda Ospedaliero-Universitaria "Maggiore della Carità", Dipartimento di Anestesia e Rianimazione, Novara, Italy - dellacorte.f@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Vaschetto
authors.forename: P
authors.initials: P
authors.lastname: Navalesi
authors.forename: N
authors.initials: N
authors.lastname: Clemente
authors.forename: E
authors.initials: E
authors.lastname: Boggio
authors.forename: S
authors.initials: S
authors.lastname: Valsecchi
authors.forename: C
authors.initials: C
authors.lastname: Olivieri
authors.forename: M F
authors.initials: MF
authors.lastname: Soluri
authors.forename: V
authors.initials: V
authors.lastname: Kroumova
authors.forename: P
authors.initials: P
authors.lastname: Fonio
authors.forename: C
authors.initials: C
authors.lastname: Dinatale
authors.forename: S
authors.initials: S
authors.lastname: Borrè
authors.forename: G
authors.initials: G
authors.lastname: Fortina
authors.forename: D
authors.initials: D
authors.lastname: Umberto
authors.forename: F
authors.initials: F
authors.lastname: Della Corte
authors.forename: A
authors.initials: A
authors.lastname: Chiocchetti
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D002116:Calcitonin / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D053495:Osteopontin / Q000494:pharmacology*; D011446:Prospective Studies; D055293:Receptors, Urokinase Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D012772:Shock, Septic / Q000097:blood
chemical_list: D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D053495:Osteopontin; D002116:Calcitonin