Comparative analyses of osteotropic human breast cancer cells in response to a bisphosphonate drug

Of those women who progress to an advanced stage of breast cancer, over 80% will develop bone metastases. Currently, bisphosphonates are used for the treatment of metastatic bone disease. Our preliminary results indicate that zoledronic acid directly acts on osteotropic cells by inhibiting angiogenesis and proliferation, and inducing cell death. In this project we used a proteomic approach to define the differences between (MDA-MB-231) and its osteotropic clone (MDA-231 BO) before and after treatment with zoledronic acid. We hypothesize that the osteotropic cells have properties that are more consistent with osteoclast-like cells. Our results indicate a concentration of 200 ?M ZA induced a strong cell death in 70-80% cells within 48 hr. Cells were then treated for 48 hr and the mitochondria fraction was extracted from both treated and non-treated cell lines. Extracted proteins were separated by SDS-PAGE and 2-dimensional gel electrophoresis. Finally differentially expressed proteins were identified using a MALDI-TOF Mass Spectrometer.