Since most cancer incidence is related to the accumulation of gene mutations, 1) the majority of cancer patients are of the elderly generation and cancer is the highest cause of death for them. These generations are often referred to as "cancer age" and cancer seems to be one of the age-related diseases.
2)On the other hand, cancer development is known to depend on the surrounding host environment.3) For example, tumor cell growth in the young is faster than that in the aged due to alterations in host factors. 4,5) Thus, it is possible that the aging process also affects cancer development by alteration of the host environment. 6,7) Cancer metastasis is often the critical trigger for the death of a patient. It begins to dissociate from primary sites and culminates with the formation of metastatic colonization.
8)These processes are very sensitive to the surrounding host factors such as the host resistance to cancerous cells. In a previous study, we suggested that it is a critical step for tumor cells in experimental tumor metastasis to avoid the host immune surveillance associated with immune cells such as natural killer (NK) cells and macrophages.9) Because the early accumulation of metastatic tumor cells in the target organ well reflected the eventual tumor metastasis, it was demonstrated that the immune system functioned to remove the tumor cells from the bloodstream and the target site in the early stage of tumor metastasis.10) From these observations, we speculated that the experimental metastatic potential would be altered with age due to the age-dependent alteration of host resistance to the metastatic tumor cells. In the present study, we investigated the alteration of experimental tumor metastasis between young and aged mice using senescenceaccelerated mice (SAM).The SAM prone (SAMP) strain was originally established as a mouse model for aging research 11,12) and shows a more accelerated senescence process than normal mouse, such as a shorter lifespan, a compromised immune system, and development of several geriatric disorders which are frequently observed in aged humans.12,13) Thus, we theorized that aged SAMP was a more appropriate model for cancer research than the young healthy mice usually used in experimental models. We used one of the SAMP strains, SAMP10, which showed several geriatric disorders such as brain atrophy. 14,15) In the present study, we investigated the alteration of tumor metastatic potential with age in those mice: 2-month-old SAMP10 was used as the "young" model and an 8-monthold as the "aged". Alteration of the NK activity with age was first examined, because NK cells are well known to work on the first line of defense against mutant cells such as cancerous cells. 16,17) Next, we investigated the early accumulation of highly lung-metastatic K1735M2 melanoma cells in the target organ using positron emission tomography (PET) and the 5-[
MATERIALS AND METHODSAnimals Senescence-accelerated mouse prone 10 (SAMP10) was purchased from Japan SLC Inc. (Shizuoka, Japan). Two-month-old SA...