Article

Journal of Mammary Gland Biology and Neoplasia

, Volume 7, Issue 2, pp 147-162

First online:

The Macrophage Growth Factor CSF-1 in Mammary Gland Development and Tumor Progression

  • Elaine Y. LinAffiliated withCenter for Study of Reproductive Biology and Women's Health, and the Departments of Developmental and Molecular Biology and Obstetrics and Gynecology and Women's Health, Albert College of Medicine
  • , Valerie Gouon-EvansAffiliated withCenter for Study of Reproductive Biology and Women's Health, and the Departments of Developmental and Molecular Biology and Obstetrics and Gynecology and Women's Health, Albert College of Medicine
  • , Andrew V. NguyenAffiliated withCenter for Study of Reproductive Biology and Women's Health, and the Departments of Developmental and Molecular Biology and Obstetrics and Gynecology and Women's Health, Albert College of Medicine
  • , Jeffrey W. PollardAffiliated withCenter for Study of Reproductive Biology and Women's Health, and the Departments of Developmental and Molecular Biology and Obstetrics and Gynecology and Women's Health, Albert College of Medicine

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Abstract

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.

CSF-1 macrophages mammary malignant osteopetrotic