"Breast cancer metastasis is a foreboding and prevalent disease for women around the world. Over 90% of breast cancer deaths are caused by metastatic disease emphasizing the urgency for more research in this area. While experimental evidence indicates that tumor cells must acquire specific genetic mutations to disseminate and colonize distant organs, these genetic alterations are not sufficient for successful metastasis formation. The microenvironment of metastatic organs must also be pre-conditioned and adapted prior to the arrival of tumor cells. In other words, metastasis is not a passive event – a ‘pre-metastatic niche’ must be established. Bone marrow-derived cells (BMDCs) play a critical role in this process by secreting soluble factors to direct the recruitment of disseminated tumor cells to specific sites. Experimental studies suggest that both innate and adaptive immune cells initiate the pre-metastatic niche, but involvement of particular BMDC populations is largely dependent on tumor type. Together, these data support the hypothesis that breast cancer metastasis is not a passive event, but is regulated by specific BMDC populations in target organs. The overall goal of this application is to examine the cellular and molecular changes that occur in pre-metastatic organs and determine which are crucial for metastasis formation using a novel breast cancer metastasis model developed by the Host laboratory. To assess this, I propose to 1) Perform an in depth kinetic characterization of disseminated tumor cell colonization of distant metastatic organs; and 2) Determine which BMDC population regulates the pre-metastatic niche and their functional significance to metastasis formation. Evaluating the specific role of BMDCs in the initiation of metastases will identify novel targets for breast cancer patients to prevent future metastatic development and/or combat established metastases."