Differential growth of IFN-beta-engineered tumor cells in nude and IFN receptor-null mice.

Abstract

The purpose of this study was to investigate the therapeutic potential of interferon-beta (IFN-beta) against tumors that resist its antiproliferative effects. Mouse fibrosarcoma cells (UV-2237m-P) and their counterparts, transfected with either IFN-beta cDNA (UV-2237m-IFN-beta) or its control vector (UV-2237m-neo), were used in the study. UV-2237m-IFN-beta cells, still expressing functional IFN receptors, were resistant to the antiproliferative effects of IFN-beta. UV-2237m-P and UV-2237m-neo cells produced progressive tumors in both nude and IFN receptor-null nude (IFNAR-/-nude) mice. In contrast, growth of UV-2237m-IFN-beta cells was significantly delayed in nude mice. UV-2237m-IFN-beta tumors from nude mice contained fewer microvessels, fewer proliferating cells, and more apoptotic cells than did UV-2237m-P and UV-2237m-neo tumors. They expressed high levels of inducible nitric oxide synthase (iNOS) and were densely infiltrated by macrophages. Incubation with macrophages from nude mice, but not those from IFNAR-/- nude mice or iNOS-null/nude mice, led to more significant killing of UV-2237m-IFN-beta cells than that of control cells, which was blocked by iNOS inhibitor N-methylarginine. Similarly, more UV-2237m-IFN-beta cells were killed when they were incubated with spleen lymphocytes from nude mice. These data indicate that IFN-beta can inhibit growth of IFN-beta-resistant tumors by T cell-independent host-mediated mechanisms, including the role of macrophages, natural killer (NK) cells, and iNOS activity.

• Authors: Fahao Zhang, Juwon Lee, Daren Wang, Zhongyun Dong
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 26 Issue 2 Pg. 108-18 (Feb 2006) ISSN: 1079-9907 [Print] United States
• PMID: 16487031 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interferon
• Interferon-beta

Topics

• Animals
• Cell Line, Tumor
• Cytotoxicity, Immunologic
• Female
• Interferon-beta (physiology)
• Killer Cells, Natural (immunology)
• Lung Neoplasms (genetics, metabolism, pathology)
• Macrophages, Peritoneal (immunology)
• Mice
• Mice, Knockout
• Mice, Nude
• Neovascularization, Pathologic (metabolism)
• Receptors, Interferon (biosynthesis, deficiency, genetics)