Intact nitric oxide synthase II gene is required for interferon-β-mediated suppression of growth and metastasis of pancreatic adenocarcinoma

Previous studies have shown that enforced expression of IFN-β suppressed tumor growth and metastasis. In this report, we determined whether the induction of nitric oxide synthase II (NOS II) gene is required for IFN-β-mediated antitumor activity using syngeneic mice with intact (NOS II^+/+) or genetically disrupted (NOS II^-/-) NOS II gene. PANC02-H7 highly metastatic murine pancreatic adenocarcinoma cells were transfected with an IFN-β expression vector or a control pcDNA3 vector. The parental PANCO2-H7, control vector-transfected, and IFN-β-transfected cells were orthotopically implanted into the pancreas of syngeneic NOS II^+/+ and NOS II^-/- C57BL/6J mice. In NOS II^+/+ C57BL/6J, both parental and control vector-transfected cells grew progressively in pancreas and produced numerous liver metastases and a large amount of malignant ascites, whereas IFN-β-secreting cells did not. In NOS II^-/- C57BL/6J mice, however, IFN-β-secreting cells grew much more aggressively. Higher NO induction was detected in NOS II^+/+ mice that received injections with lFN-β-secreting cells than with the control cells, but it was not detected in NOS II^-/- mice. These data suggested that IFN-β secreted from tumor cells stimulates NO production by host cells and suppresses tumor growth and metastasis.