Breast Cancer Metastasis to Bone Affects Osteoblast Differentiation
Annual summary rept. 15 Apr 2003-14 Apr 2004
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 mature function. Using an osteoblast cell line and metastatic breast cancer cells, we found that conditioned medium from breast cancer cells inhibited osteoblast differentiation, as demonstrated by an inhibition of alkaline phosphatase, bone sialoprotein, and osteocalcin mRNA expression, and an inhibition of mineralization. We found that these effects on differentiation are mediated through TGFbeta present in the conditioned medium. We also found that MDA-MB-231 conditioned medium altered osteoblast adhesion. Over the next year, we will further characterize these observations.
- Medicine and Medical Research