Increased breast cancer-associated metastasis in PyV MT mice induced to develop arthritis (49.3)

Abstract

Abstract We determined if inflammation caused by collagen induced arthritis in the PyV MT mice that develop spontaneous mammary gland tumor increases secondary metastasis. The PyV MT mice were injected with 2mgs/ml Type II collagen to induce arthritis at two time points, at 9 and 18 weeks of age for pre-metastatic and metastatic conditions respectively. At both time points, data demonstrated a significantly higher primary tumor burden and a 2-fold increase in lung metastasis in the arthritic versus non-arthritic PyV MT mice. Increased COX2 and CD31 staining in the bones of arthritic PyV MT mice correlated with increase in epithelial metastatic cells in the bone marrow (BM) of these mice compared to non-arthritic PyV MT. We noted increased levels of myeloid suppressor cells in the BM and decreased levels of natural killer cells in the tumor microenvironment of the arthritic versus non-arthritic PyV MT mice. Subsequent increase in circulating levels of proinflammatory cytokines, in particular prostaglandin E2, IL-6, IL-17, vascular endothelial growth factor and tumor necrosis factor-α were found to be the underlying factors contributing to the increased metastasis. The data clearly shows that breast cancer associated metastasis is increased in arthritic conditions and the data have important clinical implications especially in the prevention of secondary metastasis. Supported by DOD BCO63396