Transforming growth factor-beta1 acts as a potent inhibitor of complement C3 biosynthesis in human pancreatic cancer cell lines.

In this study, we attempted to determine how transforming growth factor (TGF)-beta1 affects complement C3 secretion in the pancreatic cancer cell lines PANC-1 and BxPC-3. We also compared the responses in C3 secretion with those in interleukin (IL)-8 secretion. The C3 and IL-8 expression was evaluated at the protein and messenger RNA (mRNA) levels. The activation of nuclear factor-kappaB (NF-kappaB) was assessed by an electrophoretic gel mobility shift assay (EMSA). IL-1beta and tumor necrosis factor (TNF)-alpha both induced a marked increase in C3 and IL-8 secretion. However, TGF-beta1 potently decreased the IL-1beta- and TNF-alpha-induced C3 secretion, whereas the IL-8 secretion was weakly but significantly enhanced. These responses were also observed at the mRNA level. In PANC-1 cells, IL-1beta and TNF-alpha induced a rapid activation of nuclear factor (NF)-kappaB, and TGF-beta1 enhanced this activation slightly. The induction of Fos protein has been reported to be required for the inhibitory action of TGF-beta1, and the translocation of Fos protein into the nucleus was associated with TGF-beta1 stimulation in PANC-1 cells. Our results suggest that TGF-beta1 may act as a potent inhibitor of C3 secretion in pancreatic cancer cell lines under inflammatory conditions. This action of TGF-beta1 did not correlate with NF-kappaB activation, but associated with the translocation of Fos protein into the nucleus.