Suppression of tumorigenicity and metastasis in murine UV-2237 fibrosarcoma cells by infection with a retroviral vector harboring the interferon-beta gene

In this study, we endeavored to determine the effectiveness of interferon beta (IFN beta) gene therapy against highly metastatic murine UV-2237m fibrosarcoma cells. UV-2237m cells were engineered to produce murine IFN beta constitutively following infection by a retroviral vector harboring the murine IFN beta gene. Parental (UV-2237m-P), control-vector-transduced (UV-2237m-Neo), and IFN beta-transduced (UV-2237m-IFN beta) cells were injected subcutaneously (s.c.) or intravenously (i.v.) into syngeneic mice. Parental and control-transduced cells produced rapidly growing tumors, whereas IFN beta-transduced cells did not. The tumorigenicity of IFN beta-sensitive or -resistant parental cells was significantly suppressed when they were injected s.c. together with IFN beta-transduced cells. The IFN beta-transduced cells did not inhibit growth of parental cells injected s.c. at a distant site. UV-2237m-IFN beta cells produced s.c. tumors in nude, SCID/Beige, and natural killer(NK)-cell-compromised syngeneic mice. The IFN beta-transduced cells were more sensitive to in vitro splenic cell-mediated lysis than were the parental or control-transduced cells. Pretreatment of C3H/HeN mice with the NK-cell-selective antiserum (anti-asialoGM1) partially abrogated the cytotoxic activity of the cells. Cytotoxic activity was not observed in mixed culture of UV-2237m-IFN beta cells and splenic cells from SCID/Beige mice. Significant cytotoxicity against UV-2237m-IFN beta cells was mediated by macrophages activated by either IFN gamma, lipopolysaccharide, or a combination of both. Our data led us to conclude that the constitutive expression of IFN beta can suppress tumorigenicity and metastasis of UV-2237m cells, which is due, in part, to activation of host effector cells.