title: TGF-β1 increases invasiveness of SW1990 cells through Rac1/ROS/NF-κB/IL-6/MMP-2.
abstract: 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.
authors.affiliation: Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Binker
authors.forename: Andres A
authors.initials: AA
authors.lastname: Binker-Cosen
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.forename: Rodica H
authors.initials: RH
authors.lastname: de Cosen
authors.forename: Laura I
authors.initials: LI
authors.lastname: Cosen-Binker
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D053773:Transforming Growth Factor beta1; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020778:Matrix Metalloproteinase 2; D020830:rac1 GTP-Binding Protein