Breast cancer-related deaths are due to the spreading of the primary tumor to other tissues and the formation of secondary tumors. This tumor spread requires specific proteins implicated in the control of cellular motility.  Interestingly, a large proportion of breast cancer overexpress the extracellular matrix protein Periostin/OSF-2. Periostin (Postn) is a secreted protein capable of increasing cell motility and stimulating blood vessel formation.  This proposal will investigate the effects of Postn gene deletion on breast cancer progression and focus on understanding the molecular mechanisms by which Postn contributes to ErbB2-driven tumorigenesis. We will then evaluate the therapeutic use of neutralizing anti-periostin antibodies in an animal model of breast cancer.