Abstract
Synergistic induction of the inducible nitric oxide synthase (NOS II) gene requires a combination of interferon-γ (IFN-γ) and lipopolysaccharide (LPS). In this study, we determined whether the induction of IFN-γ 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-γ+/+ and IFN-γ-/- mice. These cells grew and produced metastases and ascites in IFN-γ+/+ 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-γ-/- mice. Also, induction of IFN-γ correlated with NOS II gene expression and NO production in IFN-γ+/+ injected with the tumor cells but not in IFN-γ-/- mice or IFN-γ+/+ mice without tumor challenge. In vitro, only LPS plus IFN-γ induced a high level of NO production and cytotoxicity against H7 cells. These data suggested that the tumor cells stimulated IFN-γ secretion from host cells, which in turn stimulated NO production by host cells and suppressed tumor growth and metastasis.
Original language | English (US) |
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Pages (from-to) | 6930-6937 |
Number of pages | 8 |
Journal | Oncogene |
Volume | 20 |
Issue number | 47 |
DOIs | |
State | Published - Oct 18 2001 |
Keywords
- Interferon-γ
- Knockout
- Metastasis
- Nitric oxide
- Pancreas
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research