Interferon-gamma (IFNgamma) is a multifunctional cytokine with antifibrotic and antiproliferative efficiency. We previously found that pancreatic stellate cells (PSC), the main effector cells in cancer-associated fibrosis, are targets of IFNgamma action in the pancreas. Applying a combined experimental and computational approach, we have demonstrated a pivotal role of STAT1 in IFNgamma signaling in PSC. Using
in vivo and
in vitro models of pancreatic cancer, we have now studied IFNgamma effects on the tumor cells themselves. We hypothesize that IFNgamma inhibits tumor progression through two mechanisms, reduction of fibrogenesis and antiproliferative effects on the tumor cells. To elucidate the molecular action of IFNgamma, we have established a mathematical model of STAT1 activation and combined experimental studies with computer simulations.
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02/10/11