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Macrophage colony stimulating factor: Not just for macrophages anymore! A gateway into complex biologies

2008; Elsevier BV; Volume: 8; Issue: 10 Linguagem: Inglês

10.1016/j.intimp.2008.04.016

1878-1705

Thomas G. Douglass, Lara Driggers, Jian Gang Zhang, Neil Hoa, Christina Delgado, Christopher Williams, Qinhong Dan, Ramón L. Sánchez, Edward W. B. Jeffes, H. Terry Wepsic, Michael P. Myers, Kirston Koths, Martin R. Jadus,

Immune cells in cancer

Macrophage colony stimulating factor (M-CSF, also called colony stimulating factor-1) has traditionally been viewed as a growth/differentiation factor for monocytes, macrophages, and some female-specific tumors. As a result of alternative mRNA splicing and post-translational processing, several forms of M-CSF protein are produced: a secreted glycoprotein, a longer secreted form containing proteoglycan, and a short membrane-bound isoform. These different forms of M-CSF all initiate cell signaling in cells bearing the M-CSF receptor, called c-fms. Here we review the biology of M-CSF, which has important roles in bone physiology, the intestinal tract, cancer metastases to the bone, macrophage-mediated tumor cell killing and tumor immunity. Although this review concentrates mostly on the membrane form of human M-CSF (mM-CSF), the biology of the soluble forms and the M-CSF receptor will also be discussed for comparative purposes. The mechanisms of the biological effects of the membrane-bound M-CSF reveal that this cytokine is unexpectedly involved in many complex molecular events. Recent experiments suggest that a tumor vaccine based on membrane-bound M-CSF-transduced tumor cells, combined with anti-angiogenic therapy, should be evaluated further for use in clinical trials.