The development of sexual dimorphism in natural killer cell activity and resistance to tumor metastasis in the Fischer 344 rat.

The development of sexual dimorphism in the number and activity level of natural killer (NK) cells was studied in the inbred Fischer 344 rat from prepubescence to maturity. Additionally, in view of the biological significance of NK cells in controlling cancer, especially the metastatic process, we used a syngeneic mammary tumor (MADB106) to assess the host anti-metastatic activity. This tumor model was used because NK cells control the lung clearance of i.v.-injected MADB106 tumor cells, a process that critically affects the metastatic colonization of these tumor cells in the lungs. The results indicated that although prepubescent (36 days of age) males and females exhibited greater NK cytotoxicity (assessed in vitro) and higher anti-metastatic activity, evidenced by fewer tumor cells retained in the lungs. On the other hand, the mature males (140-170 days of age) displayed greater LGL/NK number and activity per ml blood, retained fewer tumor cells, and developed fewer lung tumor colonies compared to the females. During early postpubescence (63 days of age), a transitional stage between prepubescence and maturity, females and males exhibited equivalent numbers of circulating LGL/NK cells, and females displayed slightly greater NK cytotoxicity per ml blood yet retained somewhat greater numbers of tumor cells compared to the males. Overall, whereas the males exhibited increasing levels of NK number and activity throughout the age span tested, the females, despite displaying greater NK function compared to the males at prepubescence and slight improvement at postpubescence, fell behind the males in these indices of NK function at maturity.