Arthritis augments breast cancer metastasis: role of mast cells and SCF/c-Kit signaling

摘要: Breast cancer remains the second leading cause of cancer-related deaths for women in United States. Metastasis is regulated not only by intrinsic genetic changes malignant cells, but also microenvironment, especially those associated with chronic inflammation. We recently reported that mice autoimmune arthritis have significantly increased incidence bone and lung metastasis decreased survival breast cancer. In this study, we evaluated mechanism underlying metastasis. used two mouse models; one develops spontaneous (SKG mice) injected metastatic cells (4T1), another (MMTV-PyV MT type II collagen to induce arthritis. Mast cell levels were monitored. First, confirmed tumor-bearing arthritic a higher than do their nonarthritic counterparts. Next, showed recruitment mast within primary tumor mice, which facilitates report without any tumors numbers bones lungs, may be enhanced metastases observed mice. once populate niches (bones lungs), they further increase population niche assist enhancing This primarily due interaction c-Kit receptor present on stem factor (SCF, ligand ckit) expressed cells. Finally, targeting SCF/cKit an anti-ckit antibody reduces differentiation consequently first show play critical role remodeling microenvironment facilitate efficient through