Breast Cancer Metastasis to Bone Affects Osteoblast Differentiation
PENNSYLVANIA STATE UNIV UNIVERSITY PARK
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Breast cancer fatally metastasizes to bone and activates osteoclasts, cells that resorb bone, resulting in the formation of osteolytic lesions. Certain drugs, bisphosphonates, slow the action of osteoclasts, however, the bone lesions are not repaired. The osteoblasts should be able to repair the lesions by synthesizing new bone matrix. Instead, these cells appear to be inactivated by breast cancer, and the lesions do not heal. The purpose of this proposal is to understand what happens to osteoblasts in the presence of breast cancer. We hypothesize that breast cancer cells prevent pre- osteoblasts from completely maturing to osteoblasts. Our goals are to examine the effects of breast cancer cells on osteoblast proliferation, differentiation, and tnature function. Using an osteoblast cell line and metastatic breast cancer cells, we found that conditioned medium from breast cancer cells upregulated osteoblast proliferation, inhibited alkaline phosphatase activity, and blocked mineralization. Over the next two years, we will continue to examine the cause of these effects in detail. By understanding the effects of breast cancer on osteoblast differentiation, we will gain insight into how breast cancer cells alter osteoblast function. With this information, new drugs or therapies can be developed to activate osteoblasts in order to heal the bone lesions.
- Medicine and Medical Research