The development of bone metastasis from breast cancer is a common and fatal complication of the disease.Understanding the biological mechanisms underpinning this process will be vital to the development of effective treatment modalities.The development of bone metastasis involves a complex series of events including bone homing, migration and invasion.Many of these events may be orchestrated by interactions of breast ceils with specialized bone stromal components.We have developed an innovative co-culture system composed of breast cancer cells grown in association with bone stromal cells (BSCs) derived from orthopedic bone reamings from.cancer free patients.This system enables in-vitro study of the interactions of breast cells and benign bone stromal cells.We have shown that primary bone derived stromal cell cultures are superior to HS68 fibroblast culturesin stimulating migration of MCF-7 and MDAMB-231 breast cancer cells in transwell migration assays.We have used this system for discovery gene expression profiling and preliminary cytokine screening studies.This in-vitro system provides an ideal pre-clinical model to identify the molecular mechanisms of invasion and colony formation, and a system to both identify and evaluate the effects of targeting candidate molecular signaling pathways with novel therapeutics.