The macrophage growth factor CSF-1 in mammary gland development and tumor progression

Colony stimulating factor 1 (CSF-1), a major regulator of the mononuclear phagocytic lineage, is expressed in more than 70% of human breast cancers and its expression is correlated with poor prognosis. Studies of CSF-1 null mutant mice demonstrated that CSF-1 plays an important role in normal mammary ductal development as well as in mammary tumor progression to metastasis. CSF-1 regulates these processes through the recruitment and regulation of macrophages, cells that become associated with mammary tumors and the terminal end buds at the end of the growing ducts. This phenomenon suggests that the tumors subvert normal developmental processes to allow invasion into the surrounding stroma, a process that gives the tumor access to the vasculature and consequently the promotion of metastasis. In addition, soluble CSF-1 secreted from the tumor acts to divert antitumor macrophage responses and suppresses the differentiation of mature tumor-antigen-presenting dendritic cells. This review discusses these observations in detail and attempts to fit them into a larger picture of CSF-1 and macrophage action in the regulation of normal mammary gland development and tumor progression.