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BACKGROUND
The death ligand, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), induces apoptosis and non-apoptotic signaling in some tumor cells. The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors, TRAIL-R1 and TRAIL-R2, as well as Bcl-xL and TRAF2 in TRAIL-induced expression of the pro-inflammatory cytokine IL-8 and the invasion-promoting protein urokinase (uPA) in pancreatic ductal adenocarcinoma (PDAC) cells.METHODS
Colo357wt, Colo357/TRAF2, Colo357/Bcl-xL, Panc89 and PancTuI cells were stimulated with TRAIL and uPA and IL-8 expression was detected using real-time PCR. Antagonistic, receptor-specific antibodies were used to investigate the effects of TRAIL-R1 or TRAIL-R2 inhibition.RESULTS
Dose-dependent increases in uPA and IL-8 expression were detected following TRAIL stimulation in PDAC cells. These effects were inhibited when TRAIL-R1 but not TRAIL-R2 was blocked. Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL-mediated upregulation of uPA and IL-8.CONCLUSIONS
In PDAC cells, TRAIL strongly induced uPA and IL-8 via TRAIL-R1. This response was further enhanced in cells overexpressing TRAF2 and Bcl-xL. Therefore, inhibition of the non-apoptotic "side-effects" of TRAIL treatments by inactivation of TRAF2 and Bcl-xL might represent additional relevant strategies for the treatment of pancreatic cancer.
uPA → TRAIL: " TRAIL induced expression of uPA and IL-8 strongly enhanced by overexpression of TRAF2 and Bcl-xL in pancreatic ductal adenocarcinoma cells "
IL-8 ⊣ Bcl-xL: " The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors, TRAIL-R1 and TRAIL-R2, as well as Bcl-xL and TRAF2 in TRAIL induced expression of the pro-inflammatory cytokine IL-8 and the invasion promoting protein urokinase ( uPA ) in pancreatic ductal adenocarcinoma ( PDAC ) cells "
IL-8 ⊣ TRAIL: " The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors, TRAIL-R1 and TRAIL-R2, as well as Bcl-xL and TRAF2 in TRAIL induced expression of the pro-inflammatory cytokine IL-8 and the invasion promoting protein urokinase ( uPA ) in pancreatic ductal adenocarcinoma ( PDAC ) cells "
IL-8 ⊣ TRAF2: " The purpose of this study was to investigate the roles of the pro-apoptotic TRAIL receptors, TRAIL-R1 and TRAIL-R2, as well as Bcl-xL and TRAF2 in TRAIL induced expression of the pro-inflammatory cytokine IL-8 and the invasion promoting protein urokinase ( uPA ) in pancreatic ductal adenocarcinoma ( PDAC ) cells "
IL-8 ⊣ Bcl-xL: " Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL mediated upregulation of uPA and IL-8 "
IL-8 ⊣ TRAF2: " Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL mediated upregulation of uPA and IL-8 "
uPA ⊣ Bcl-xL: " Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL mediated upregulation of uPA and IL-8 "
uPA ⊣ TRAF2: " Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL mediated upregulation of uPA and IL-8 "
IL-8 → TRAIL: " Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL mediated upregulation of uPA and IL-8 "
uPA → TRAIL: " Overexpression of TRAF2 or Bcl-xL strongly increased TRAIL mediated upregulation of uPA and IL-8 "
TRAIL → IL-8: " In PDAC cells, TRAIL strongly induced uPA and IL-8 via TRAIL-R1 "
TRAIL → uPA: " In PDAC cells, TRAIL strongly induced uPA and IL-8 via TRAIL-R1 "