Abstracts
1997 Digestive Disease Week

Interleukin-1ß upregulates urokinase-type plasminogen activator in human pancreatic carcinoma.

J Vogel, D Albo, H Chang, DH Berger. Allegheny University of the Health Sciences, MCP*Hahnemann School of Medicine, Philadelphia, PA.

Plasmin mediated degradation of the extracellular matrix is important in tumor invasion. The plasmin-protease system is tightly regulated by the expression of uPA and its natural inhibitor, type one plasminogen activator inhibitor (PAI-1). IL-1ß, an important inflammatory cytokine which is overexpressed in pancreatic cancer, may function in part by upregulating uPA expression. We hypothesized that in pancreatic cancer IL-1ß up-regulates plasmin-protease activity by stimulating the expression of uPA in the absence of co-stimulation of PAI-1. ASPC-1 cells were grown to 80-90% confluence in media with 10% FCS. Media was changed and cells were grown serum free for an additional 8 hours. Cells were then treated for 24 hours with either control or IL-1ß (1, 10, 100 units/ml). The conditioned media was collected, cell extracts prepared, and uPA and PAI-1 protein was measured by ELISA. Treatment with IL-1ß resulted in a significant, dose dependent increase in the production of uPA (Figure 1 [not available]). There was no significant effect of IL-1ß on the production of PAI-1 (Figure 2 [not available]).

These data demonstrate that IL-1ß up-regulates the expression of uPA in pancreatic cancer cells in the absence of a concommitant increase in PAI-1 expression. Differential regulation of the plasmin protease system in pancreatic cancer by IL-1ß may result in increased peritumoral proteolytic activity and enhanced invasion and metastasis.