Abstract # 1779 Select behavioral and physiological changes persist in novel cancer survivor model

Abstract

Even after successful cancer treatment, survivors report distinct physical and mental health problems, which reduce quality of life. Little is known about the mechanisms underlying the enduring neurobehavioral consequences of a former cancer experience. The objective of this project was to develop a tumor-resected “survivor” mouse model by which to investigate these persistent effects. We hypothesized that mouse mammary tumors induce neuroinflammation, increase affective-like behaviors, and cognitive function, all of which are attenuated by tumor resection. Murine cancer cells (67NR) were injected into mammary fat pads of 9-week old, group-housed anesthetized female Balb/c mice. Non-tumor controls underwent sham surgery. Body mass and tumor size were recorded biweekly. These tumors are non-metastatic and after 2 weeks (tumors ∼ 0.75 cm3), tumors in some mice were surgically resected (“survivor” group) with clean margins (no recurrence). Two weeks after these treatments (sham, tumor, tumor resection), all mice were tested using a battery of standardized behavioral tests. To assess immune activation, inflammatory gene expression was quantified in various brain regions, as well as circulating inflammatory markers and immune cells. Preliminary results indicate that tumor resection attenuated IL-1beta expression in the hippocampus and specific peripheral immune measures. However, circulating immune cell trafficking and behavior did not return to levels of tumor-free control mice, suggesting that the influence of tumors endures. These immune changes may mediate prolonged behavioral comorbidities.