Age-related decrease of pulmonary metastasis of rat mammary carcinoma by activated natural resistance.

We found that the number of pulmonary metastatic foci of spontaneously developed rat mammary carcinoma (SST-2), when transplanted subcutaneously in spontaneously hypertensive (SH) rats, decreased with aging. In the SST-2-bearing SH rats, it was observed that T cell functions progressively declined while activities of macrophages and natural killer cells were non-specifically activated by increasing age. To examine the mechanisms of the age-related decrease of pulmonary metastasis in SH rats, we treated the SST-2-bearing rats with anti-(asialo-GM1) antibody and/or carrageenan, which are known to suppress the functions of macrophages and natural killer cells, or with poly(I).poly(C), which is a stimulator to natural killer cells. The anti-(asialo-GM1) treatment significantly increased the number of pulmonary metastatic foci in both young and old SH rats, while poly(I).poly(C) significantly decreased the lung nodules in the old SH rats. These result suggest that the decrease of pulmonary metastasis in the SH rats with aging may be closely correlated with non-specifically activated natural killer cells and macrophages, though it should be also considered that non-immunological tumor-host interactions may be involved in the differences between the young and the old SH rats.