کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1930624 | 1050520 | 2011 | 6 صفحه PDF | دانلود رایگان |
Human pancreatic cancer invasion and metastasis have been found to correlate with increased levels of active matrix metalloproteinase 2 (MMP-2). The multifunctional cytokine transforming growth factor beta 1 (TGF-β1) has been shown to increase both secretion of MMP-2 and invasion by several pancreatic cancer cell types. In the present study, we investigated the signaling pathway involved in TGF-β1-promoted MMP-2 secretion and invasion by human pancreatic cancer cells SW1990. Using specific inhibitors, we found that stimulation of these tumor cells with TGF-β1 induced secretion and activation of the collagenase MMP-2, which was required for TGF-β1-stimulated invasion. Our results also indicate that signaling events involved in TGF-β1-enhanced SW1990 invasiveness comprehend activation of Rac1 followed by generation of reactive oxygen species through nicotinamide adenine dinucleotide phosphate-oxidase, activation of nuclear factor-kappa beta, release of interleukin-6, and secretion and activation of MMP-2.
Research highlights
► Rac1 mediates TGF-β1-induced SW1990 invasion through MMP-2 secretion and activation.
► NADPH-generated ROS act downstream of Rac1 in TGF-β1-challenged SW1990 cells.
► TGF-β1-stimulated ROS activate NF-κB in SW1990 cells.
► NFκB-induced IL-6 release is required for secretion and activation of MMP-2 in SW1990 cells.
Journal: Biochemical and Biophysical Research Communications - Volume 405, Issue 1, 4 February 2011, Pages 140–145