Pancreatic Adenocarcinoma -mediated Suppression of Growth and Metastasis of β Gene Is Required for Interferon- Nitric Oxide Synthase II Intact

Previous studies have shown that enforced expression of IFN-b 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-b-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-b expression vector or a control pcDNA3 vector. The parental PANC02-H7, control vector-transfected, and IFN-btransfected 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-b-secreting cells did not. In NOS II C57BL/6J mice, however, IFN-b-secreting cells grew much more aggressively. Higher NO induction was detected in NOS II mice that received injections with IFN-b-secreting cells than with the control cells, but it was not detected in NOS II mice. These data suggested that IFN-b secreted from tumor cells stimulates NO production by host cells and suppresses tumor growth and metastasis.