The most common site of breast cancer metastasis is bone. The majority of these metastases are osteolytic, characterized by an increase in bone degradation via an upregulation of osteoclast activity. These effects lead to complications including fracture, contractile pain and hypercalcemia, significantly reducing the quality of life in these patients. The role of bone forming osteoblasts at sites of osteolytic lesions is less understood. We have recently shown that breast cancer cells are capable of inducing apoptosis of osteoblasts in vitro as well as in vivo using murine xenograft models. This effect would further exacerbate osteolytic disease, and may explain why treatment strategies capable of inhibiting osteolysis (bisphosphonates) are not capable of repairing lost bone. We hypothesize that modulating the number of osteoblasts at sites of osteolytic metastases, may aid in the repair of resorbed bone. To provide proof-of-principle evidence, we have engineered the murine pre-osteoblast cell line, MC3T3-E1, to overexpress Bcl2, conferring resistance to apoptosis. These cells will be used with an in vivo model of osteolysis using GFP-labeled breast cancer cells previously reported by our laboratory. Apoptosis resistant MC3T3-E1 will be injected into bone both before, and after induction of osteolysis and rates of bone resorption and repair will be measured. The results of this project will provide the first in vivo evidence that restoration of osteoblasts at sites of osteolytic metastases can aid in the repair of lost bone and will test for the first time, experimental manipulation of osteoblast number and function in osteolytic breast cancer metastasis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 484.