PANCREATIC STELLATE NOX 1-DERIVED ROS FACILIATE INVASION OF PANCREATIC CANCER CELLS THROUGH MATRIX METALLOPROTEINASE 9

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a type of exocrine cancer that accounts for almost all cases of pancreatic cancer. Many studies show that chronic pancreatitis (CP), a long-term inflammation of the pancreas, is considered as the greatest risk factor for developing pancreatic cancer. We found that reactive oxygen species (ROS) generated by NADPH oxidase 1 (Nox1) in pancreatic stellate cells (PaSCs) mediate the fibrogenic process in CP. PaSCs are a class of pancreatic cells that, in the stroma surrounding pancreatic cancer cells, are known to facilitate cancer cell invasion. We found that the lack of Nox1 in PaSCs decreased the invasion of three different pancreatic cell lines using two approaches: transwell cell invasion and culture wound closure assays. The lack of Nox1 also decreased the expression of matrix metalloproteinase 9, which is an enzyme that breaks down the basal lamina, facilitating cell invasion. Using mass spectroscopy, we will assess the extent to which the lack of Nox1 in PaSCs affects the production of pro-migratory and pro-invasive proteins using mass spectroscopy. These results implicate Nox1 inhibitors as a potential therapeutic drug to impede the progression of CP to PDAC.