CHARACTERIZING THE ROLE OF PANCREATIC STELLATE CELLS IN THE TRANSITION OF CHRONIC PANCREATITIS TO PANCREATIC CANCER
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Abstract
Background- Chronic pancreatitis (CP) and pancreatic cancer are two diseases that share a mutual histological feature known as fibrosis produced by pancreatic stellate cells (PaSCs). In response to pancreatic inflammation, PaSCs are activated from quiescent phenotype into myofibroblast-like cells, which express extracellular matrix components. PaSCs are also known to facilitate the migration and invasion of pancreatic cancer cells, which are accompanied by increased matrix metalloprotease (MMP) production and epithelial-to mesenchymal transition (EMT). NADPH oxidase (Nox) is a family of enzymes that catalyze the transfer of an electron from NAD(P)H to oxygen to generate superoxide or hydrogen peroxide. Because Nox1 is expressed in PaSCs, the objective of this study was to assess the extent to which Nox1 in PaSCs facilitates the migration and invasion of pancreatic cancer cells by regulating the expression of MMP and genes involved in EMT. Results/Discussion-We found that the lack of Nox1 lowers the expression of MMP-9 mRNA and the EMT-induced gene Snail in PaSCs. Further studies need to be done in PaSCs from mice with CP and CP-associated oncogenic KRas-driven pancreatic cancer.