Alteration of Murine Mammary Tumor Metastasis and Growth by Cytomegalovirus Infection¹

Host resistance to the development of metastatic lesions is complex and involves both lymphocyte and macrophage functions. Studies in both humans and animals have suggested that cytomegalovirus infection may alter these components of the defense mechanism of the host. In the present study, an experimental model was developed to determine whether cytomegalovirus infection would affect host resistance to the establishment of metastatic tumor nodules in the lungs of C3H mice after i.v. inoculation of a single-cell suspension of mammary tumor cells. The number of tumor nodules in the lungs, the lungs-heart/body weight ratio, and the mean day of death were determined in control animals inoculated i.v. with 10⁶ mammary tumor cells and compared with groups of animals also receiving a sublethal i.p. inoculum of murine cytomegalovirus (MCMV) (10⁵ plaque-forming units) either 3 days before, on the day of, or 10 or 13 days after tumor cell inoculation. The results suggest a biphasic effect of virus infection on tumor development in the lung. A preexisting or concurrent MCMV infection suppressed tumor growth and prolonged life, while a MCMV infection later in tumorigenesis enhanced tumor growth and shortened survival. These data suggest that MCMV modulates host resistance to the development of metastatic tumor nodules and that this experimental model may be utilized to investigate further the relationship between virus-induced alterations of host defense mechanisms and tumor growth.