133. Age and psychosocial stress affect depression and anxiety-related behaviors, tumor growth and leukocyte infiltration in an orthotopic mouse model of prostate cancer

Interactions between age, psychosocial stress and prostate cancer (PCa) progression are critically understudied. Therefore, we characterized the effects of aging and psychosocial stress on anxiety/depression-like behavior, tumor growth and host defense using the immunocompetent, orthotopic, RM-9 murine PCa reconstitution model (MPR 3 ). Two- and 18-month-old tumor-bearing C57BL/6 mice were exposed to isolation and restraint stress (2 h/day) for 14 days post-tumor inoculation and compared with group-housed, non-stressed, tumor-bearing controls. Zero maze testing revealed age-related differences before tumor induction, and increased anxiety-like behavior. Open field testing showed that old non-stressed tumor-bearing mice were less active throughout the 30-min test period than young non-stressed and stressed, and old stressed tumor-bearing mice. Old mice demonstrated more depressed-like behavior than young mice with tail suspension testing, without effects of isolation/restraint stress. Old mice developed larger tumors, despite no age-related differences in tumor TGF-beta1 or VEGF levels. Tumor in young mice had more macrophages, the predominant immunocyte in tumors, and more CD4+ and CD4+FoxP3+ T-cells than old mice. Stress increased macrophage infiltration in old mice, but reduced CD4+ and CD4+FoxP3+ T-cell infiltration in young mice. CD8+ T cell infiltration was similar across treatment groups. Survival rate for old, stressed mice was 20% lower than all other groups. These findings suggest age- and stress-related differences in behavioral and immune responses in prostate tumor-bearing mice that can affect disease outcome.