| First Author | Wang B | Year | 2001 |
| Journal | Oncogene | Volume | 20 |
| Issue | 47 | Pages | 6930-7 |
| PubMed ID | 11687972 | Mgi Jnum | J:72687 |
| Mgi Id | MGI:2153400 | Doi | 10.1038/sj.onc.1204871 |
| Citation | Wang B, et al. (2001) Genetic disruption of host interferon-gamma drastically enhances the metastasis of pancreatic adenocarcinoma through impaired expression of inducible nitric oxide synthase. Oncogene 20(47):6930-7 |
| abstractText | Synergistic induction of the inducible nitric oxide synthase (NOS II) gene requires a combination of interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). In this study, we determined whether the induction of IFN-gamma was required for NOS II-mediated antitumor activity in vivo. Highly metastatic H7 murine pancreatic adenocarcinoma cells were implanted into the subcutis, footpad, and pancreas of syngeneic IFN-gamma(+/+) and IFN-gamma(-/-) mice. These cells grew and produced metastases and ascites in IFN-gamma(+/+) mice. In sharp contrast, the same tumor cells grew much more aggressively, metastasized more extensively, and produced a larger amount of malignant ascites in IFN-gamma(-/-) mice. Also, induction of IFN-gamma correlated with NOS II gene expression and NO production in IFN-gamma(+/+) injected with the tumor cells but not in IFN-gamma(-/-) mice or IFN-gamma(+/+) mice without tumor challenge. In vitro, only LPS plus IFN-gamma induced a high level of NO production and cytotoxicity against H7 cells. These data suggested that the tumor cells stimulated IFN-gamma secretion from host cells, which in turn stimulated NO production by host cells and suppressed tumor growth and metastasis. |
