Establishment of therapeutic methods against oral cancer using interferon-gamma gene

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Interferon-gamma (IFN-gamma) is an multifunctional cytokine whose major actions include inhibition of proliferation of cancer cells and regulation of the expression of some cell adhesion molecules on cancer cells. Although these functions of IFN-gamma are known to be important in host immune functions against cancer, little is known about the essential role of IFN-gamma in the course of metastasis of cancer cells. The purpose of this study is to investigate the essential role of IFN-gamma on the metastatic property of cancer cells, using IFN-gamma receptor gene knock-out mice (IFN-gamma R0/0 mice). Both wild-type (WT) and IFN-gamma R0/0 mice were injected in to the tail vein, or i.p.with 1*10_5 of B16 cells, highly metastatic melanoma cells. Three weeks after injection, mice were killed and spleens, lungs and livers were removed from both types of mice and the extent of metastasis was compared microscopically. As a results, B16 cells were more abundant in the organs removed from WT mice than there removed from IFN-gamma R0/0 mice which are injected intravenously. B16 cells were more abundant in the periotoneal cavity of WT mice than that of IFN-gamma R0/0 mice which are injected i.p. Three weeks after intravenous injection of B16 cells, serum was also separated from peripheral blood and cytokine levels were determined by ELISA.there were no statistical differences in serum levels of IL-1alpha, IL-6 and TNF between WT and IFN-gamma R0/0 mice. There were no statistical differences in serum levels of IL-1alpha, IL-6, IL-12 and TNF between WT and IFN-gamma R0/0 mice. IL-12 mRNA levels in spleen from IFN-gamma R0/0 were hihger than those in WT mice, . There was also no clear differences in serum levels of nitric oxide, a cytotoxic effector molecule of activated macrophages, between WT and IFN-gamma R0/0 mice. There results suggest that mice can resisit aganinst cancer metastasis in the absense of IFN-gamma.