Growth and Metastasis of Intraocular Tumors in Aged Mice

PURPOSE Since deterioration of the immune apparatus is closely associated with cancer, we examined the effect of aging on the growth and metastasis of intraocular melanomas in mice. METHODS Murine B16LS9 melanoma cells were transplanted into the posterior compartment of the eye (vitreous chamber) and intraocular tumor growth and development of liver metastases were evaluated in young (8-10 weeks of age) and old (>18 months of age) mice. Liver metastases were also induced by intrasplenic injection of melanoma cells. Natural killer (NK) cells from the livers of mice harboring liver metastases were evaluated in vitro for their cytolytic activity. RESULTS Tumors grew more rapidly in the eyes of young mice than old mice, yet old mice developed significantly more liver metastases. Increased liver metastasis in old mice was evident even when melanoma cells were injected intrasplenically as a means of bypassing the influence of the ocular immunosuppressive environment. Increased liver metastases in old mice correlated with reduced cytolytic activity of liver NK cells. Lethally irradiated young mice reconstituted with bone marrow from old donors developed significantly more liver metastases than young mice reconstituted with bone marrow from young donors, indicating that bone marrow-derived cells were the root cause of the heightened development of metastases in old mice. CONCLUSIONS Aging affects the growth and metastasis of intraocular melanomas. Even though intraocular melanomas grow slower in old mice, the development of liver metastases is exacerbated and correlates with a reduction in liver NK cell activity in the old mouse.