Reactivation of Breast Cancer Micrometastases by Senescent Bone Marrow Stroma.

摘要

We developed an in vitro injury model of stroma cultured from bone marrow samples of mice and human donors. We demonstrated that oxidative and hypoxic damage and estrogen deprivation can induce IL-6 and IL-8 export by human female, premenopausal stroma. We adapted a breast cancer cell co-culture model to determine effect of injury on stromal capacity to support dormancy and demonstrated that breast cancer cells induce inflammatory cytokine secretion by stroma. We adapted an osteoclast activation model to determine the capacity of injured stroma to activate osteoclasts. We also adapted a preosteoblast co- culture model to determine the role of osteoblasts in the micrometastatic cell niche. Studies on estrogen replacement and anti-inflammatory treatment will determine reversibility.