CSF-1 signaling in macrophages: pleiotrophy through phosphotyrosine-based signaling pathways

References

• Pixley FJ, Stanley ER. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol 2004;14:628–638.
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Greter M, Leboeuf M et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 2010;330:841–845.
   PubMed Web of Science ®Google Scholar
• Ginhoux F, Tacke F, Angeli V et al. Langerhans cells arise from monocytes in vivo. Nat Immunol 2006;7:265–273.
   PubMed Web of Science ®Google Scholar
• Austyn JM, Gordon S. F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 1981;11:805–815.
   PubMed Web of Science ®Google Scholar
• Hume DA. Differentiation and heterogeneity in the mononuclear phagocyte system. Mucosal Immunol 2008;1:432–441.
   PubMed Web of Science ®Google Scholar
• Niemi M, Sharpe RM, Brown WR. Macrophages in the interstitial tissue of the rat testis. Cell Tissue Res 1986;243:337–344.
   PubMed Web of Science ®Google Scholar
• Sasmono RT, Oceandy D, Pollard JW et al. A macrophage colony-stimulating factor receptor-green fluorescent protein transgene is expressed throughout the mononuclear phagocyte system of the mouse. Blood 2003;101:1155–1163.
   PubMed Web of Science ®Google Scholar
• Rae F, Woods K, Sasmono T et al. Characterisation and trophic functions of murine embryonic macrophages based upon the use of a Csf1r-EGFP transgene reporter. Dev Biol 2007;308:232–246.
   Google Scholar
• Akagawa KS. Functional heterogeneity of colony-stimulating factor-induced human monocyte-derived macrophages. Int J Hematol 2002;76:27–34.
   PubMed Web of Science ®Google Scholar
• Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005;5:953–964.
   PubMed Web of Science ®Google Scholar
• Pollard JW. Trophic macrophages in development and disease. Nat Rev Immunol 2009;9:259–270.
   PubMed Web of Science ®Google Scholar
• Stefater JAr, Ren S, Lang RA, Duffield JS. Metchnikoff’s policemen: macrophages in development, homeostasis and regeneration. Trends Mol Med 2011.
   Google Scholar
• Yoshida H, Hayashi S, Kunisada T et al. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 1990;345:442–444.
   PubMed Web of Science ®Google Scholar
• Wiktor-Jedrzejczak W, Bartocci A, Ferrante AWJ et al. Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. Proc Natl Acad Sci USA 1990;87:4828–4832.
   PubMed Web of Science ®Google Scholar
• Cecchini MG, Dominguez MG, Mocci S et al. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse. Development 1994;120:1357–1372.
   PubMed Web of Science ®Google Scholar
• Yasuda H, Shima N, Nakagawa N et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 1998;95:3597–3602.
   PubMed Web of Science ®Google Scholar
• Gouon-Evans V, Rothenberg ME, Pollard JW. Postnatal mammary gland development requires macrophages and eosinophils. Development 2000;127:2269–2282.
   PubMed Web of Science ®Google Scholar
• Pollard JW, Hennighausen L. Colony stimulating factor 1 is required for mammary gland development during pregnancy. Proc Natl Acad Sci USA 1994;91:9312–9316.
   PubMed Web of Science ®Google Scholar
• Ingman WV, Wyckoff J, Gouon-Evans V, Condeelis J, Pollard JW. Macrophages promote collagen fibrillogenesis around terminal end buds of the developing mammary gland. Dev Dyn 2006;235:3222–3229.
   PubMed Web of Science ®Google Scholar
• Cohen PE, Zhu L, Nishimura K, Pollard JW. Colony-stimulating factor 1 regulation of neuroendocrine pathways that control gonadal function in mice. Endocrinology 2002;143:1413–1422.
   PubMed Web of Science ®Google Scholar
• Tessem JS, Jensen JN, Pelli H et al. Critical roles for macrophages in islet angiogenesis and maintenance during pancreatic degeneration. Diabetes 2008;57:1605–1617.
   PubMed Web of Science ®Google Scholar
• Michaelson MD, Bieri PL, Mehler MF et al. CSF-1 deficiency in mice results in abnormal brain development. Development 1996;122:2661–2672.
   PubMed Web of Science ®Google Scholar
• Wood W, Turmaine M, Weber R et al. Mesenchymal cells engulf and clear apoptotic footplate cells in macrophageless PU.1 null mouse embryos. Development 2000;127:5245–5252.
   Google Scholar
• Yasui M, Tanaka H, Seino Y. The role of tissue-fixed macrophages in apoptosis in the developing kidney. Nephron 1997;77:325–332.
   PubMed Web of Science ®Google Scholar
• Arceci RJ, Shanahan F, Stanley ER, Pollard JW. Temporal expression and location of colony-stimulating factor 1 (CSF-1) and its receptor in the female reproductive tract are consistent with CSF-1-regulated placental development. Proc Natl Acad Sci USA 1989;86:8818–8822.
   PubMed Web of Science ®Google Scholar
• Pollard JW. Role of colony-stimulating factor-1 in reproduction and development. Mol Reprod Dev 1997;46:54–60; discussion 60.
   Google Scholar
• Chitu V, Stanley ER. Colony-stimulating factor-1 in immunity and inflammation. Curr Opin Immunol 2006;18:39–48.
   PubMed Web of Science ®Google Scholar
• Guleria I, Pollard JW. Aberrant macrophage and neutrophil population dynamics and impaired Th1 response to Listeria monocytogenes in colony-stimulating factor 1-deficient mice. Infect Immun 2001;69:1795–1807.
   Google Scholar
• Teitelbaum R, Schubert W, Gunther L et al. The M cell as a portal of entry to the lung for the bacterial pathogen Mycobacterium tuberculosis. Immunity 1999;10:641–650.
   PubMed Web of Science ®Google Scholar
• Pixley FJ, Stanley ER. Cytokines and Cytokine Receptors Regulating Cell Survival, Proliferation, and Differentiation in Hematopoiesis. In: Dennis EA, Bradshaw RA, editors. Intercellular Signaling in Development and Disease. San Diego: Academic Press; 2011. p. Chapter 319.
   Google Scholar
• Hamilton JA, Whitty G, Masendycz P et al. The critical role of the colony-stimulating factor-1 receptor in the differentiation of myeloblastic leukemia cells. Mol Cancer Res 2008;6:458–467.
   Google Scholar
• Feng R, Desbordes SC, Xie H et al. PU.1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells. Proc Natl Acad Sci USA 2008;105:6057–6062.
   PubMed Web of Science ®Google Scholar
• Koschmieder S, Rosenbauer F, Steidl U, Owens BM, Tenen DG. Role of transcription factors C/EBPalpha and PU.1 in normal hematopoiesis and leukemia. Int J Hematol 2005;81:368–377.
   PubMed Web of Science ®Google Scholar
• Sampaio NG, Yu W, Cox D et al. Phosphorylation of CSF-1R Y721 mediates its association with PI3K to regulate macrophage motility and enhancement of tumor cell invasion. J Cell Sci 2011;124:2021–2031.
   Google Scholar
• Yu W, Chen J, Xiong Y et al. CSF-1 receptor structure/function in MacCsf1r-/- macrophages: regulation of proliferation, differentiation, and morphology. J Leukoc Biol 2008;84:852–863.
   Google Scholar
• Yeung YG, Stanley ER. Proteomic approaches to the analysis of early events in colony-stimulating factor-1 signal transduction. Mol Cell Proteomics 2003;2:1143–1155.
   Google Scholar
• Stanley E, Lieschke GJ, Grail D et al. Granulocyte/macrophage colony-stimulating factor-deficient mice show no major perturbation of hematopoiesis but develop a characteristic pulmonary pathology. Proc Natl Acad Sci USA 1994;91:5592–5596.
   PubMed Web of Science ®Google Scholar
• Tushinski RJ, Oliver IT, Guilbert LJ, Tynan PW, Warner JR, Stanley ER. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell 1982;28:71–81.
   PubMed Web of Science ®Google Scholar
• Naito M, Hasegawa G, Ebe Y, Yamamoto T. Differentiation and function of Kupffer cells. Med Electron Microsc 2004;37:16–28.
   PubMedGoogle Scholar
• Stanley ER, Berg KL, Einstein DB et al. Biology and action of colony–stimulating factor-1. Mol Reprod Dev 1997;46:4–10.
   PubMed Web of Science ®Google Scholar
• Ryan GR, Dai XM, Dominguez MG et al. Rescue of the colony-stimulating factor 1 (CSF-1)-nullizygous mouse (Csf1(op)/Csf1(op)) phenotype with a CSF-1 transgene and identification of sites of local CSF-1 synthesis. Blood 2001;98:74–84.
   PubMed Web of Science ®Google Scholar
• Dai XM, Zong XH, Sylvestre V, Stanley ER. Incomplete restoration of colony-stimulating factor 1 (CSF-1) function in CSF-1-deficient Csf1op/Csf1op mice by transgenic expression of cell surface CSF-1. Blood 2004;103:1114–1123.
   PubMedGoogle Scholar
• Nandi S, Akhter MP, Seifert MF, Dai XM, Stanley ER. Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain. Blood 2006;107:786–795.
   Google Scholar
• Dai XM, Ryan GR, Hapel AJ et al. Targeted disruption of the mouse colony-stimulating factor 1 receptor gene results in osteopetrosis, mononuclear phagocyte deficiency, increased primitive progenitor cell frequencies, and reproductive defects. Blood 2002;99:111–120.
   PubMed Web of Science ®Google Scholar
• Lin H, Lee E, Hestir K et al. Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science 2008;320:807–811.
   PubMed Web of Science ®Google Scholar
• Garceau V, Smith J, Paton IR et al. Pivotal Advance: Avian colony-stimulating factor 1 (CSF-1), interleukin-34 (IL-34), and CSF-1 receptor genes and gene products. J Leukoc Biol 2010;87:753–764.
   PubMed Web of Science ®Google Scholar
• Chihara T, Suzu S, Hassan R et al. IL-34 and M-CSF share the receptor Fms but are not identical in biological activity and signal activation. Cell Death Differ 2010;17:1917–1927.
   PubMed Web of Science ®Google Scholar
• Wei S, Nandi S, Chitu V et al. Functional overlap but differential expression of CSF-1 and IL-34 in their CSF-1 receptor-mediated regulation of myeloid cells. J Leukoc Biol 2010;88:495–505.
   PubMed Web of Science ®Google Scholar
• Sherr CJ, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER. The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 1985;41:665–676.
   PubMed Web of Science ®Google Scholar
• Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2010;141:1117–1134.
   PubMed Web of Science ®Google Scholar
• Grassot J, Gouy M, Perrière G, Mouchiroud G. Origin and molecular evolution of receptor tyrosine kinases with immunoglobulin-like domains. Mol Biol Evol 2006;23:1232–1241.
   PubMed Web of Science ®Google Scholar
• Lyman SD, Jacobsen SE. c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood 1998;91:1101–1134.
   PubMed Web of Science ®Google Scholar
• Chen X, Liu H, Focia PJ, Shim AH, He X. Structure of macrophage colony stimulating factor bound to FMS: diverse signaling assemblies of class III receptor tyrosine kinases. Proc Natl Acad Sci USA 2008;105:18267–18272.
   PubMed Web of Science ®Google Scholar
• van der Geer P, Hunter T. Identification of tyrosine 706 in the kinase insert as the major colony-stimulating factor 1 (CSF-1)-stimulated autophosphorylation site in the CSF-1 receptor in a murine macrophage cell line. Mol Cell Biol 1990;10:2991–3002.
   PubMedGoogle Scholar
• Tapley P, Kazlauskas A, Cooper JA, Rohrschneider LR. Macrophage colony-stimulating factor-induced tyrosine phosphorylation of c-fms proteins expressed in FDC-P1 and BALB/c 3T3 cells. Mol Cell Biol 1990;10:2528–2538.
   PubMedGoogle Scholar
• Wilhelmsen K, Burkhalter S, van der Geer P. C-Cbl binds the CSF-1 receptor at tyrosine 973, a novel phosphorylation site in the receptor’s carboxy-terminus. Oncogene 2002;21:1079–1089.
   PubMedGoogle Scholar
• Joos H, Trouliaris S, Helftenbein G, Niemann H, Tamura T. Tyrosine phosphorylation of the juxtamembrane domain of the v-Fms oncogene product is required for its association with a 55-kDa protein. J Biol Chem 1996;271:24476–24481.
   PubMed Web of Science ®Google Scholar
• Mancini A, Niedenthal R, Joos H et al. Identification of a second Grb2 binding site in the v-Fms tyrosine kinase. Oncogene 1997;15:1565–1572.
   PubMed Web of Science ®Google Scholar
• Schlessinger J, Lemmon MA. SH2 and PTB domains in tyrosine kinase signaling. Sci STKE 2003;2003:RE12.
   PubMedGoogle Scholar
• Hamilton JA. CSF-1 signal transduction. J Leukoc Biol 1997;62:145–155.
   PubMed Web of Science ®Google Scholar
• Suzuki H, Forrest AR, van Nimwegen E et al. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line. Nat Genet 2009;41:553–562.
   PubMedGoogle Scholar
• Bourette RP, Rohrschneider LR. Early events in M-CSF receptor signaling. Growth Factors 2000;17:155–166.
   PubMed Web of Science ®Google Scholar
• Hubbard SR. Juxtamembrane autoinhibition in receptor tyrosine kinases. Nat Rev Mol Cell Biol 2004;5:464–471.
   PubMed Web of Science ®Google Scholar
• Alonso G, Koegl M, Mazurenko N, Courtneidge SA. Sequence requirements for binding of Src family tyrosine kinases to activated growth factor receptors. J Biol Chem 1995;270:9840–9848.
   PubMed Web of Science ®Google Scholar
• Rohde CM, Schrum J, Lee AW. A juxtamembrane tyrosine in the colony stimulating factor-1 receptor regulates ligand-induced Src association, receptor kinase function, and down-regulation. J Biol Chem 2004;279:43448–43461.
   Google Scholar
• Xiong Y, Song D, Cai Y, Yu W, Yeung YG, Stanley ER. A CSF-1 receptor phosphotyrosine 559 signaling pathway regulates receptor ubiquitination and tyrosine phosphorylation. J Biol Chem 2011;286:952–960.
   Google Scholar
• Hong L, Munugalavadla V, Kapur R. c-Kit-mediated overlapping and unique functional and biochemical outcomes via diverse signaling pathways. Mol Cell Biol 2004;24:1401–1410.
   PubMedGoogle Scholar
• Takeshita S, Faccio R, Chappel J et al. c-Fms tyrosine 559 is a major mediator of M-CSF-induced proliferation of primary macrophages. J Biol Chem 2007;282:18980–18990.
   PubMedGoogle Scholar
• Baruzzi A, Caveggion E, Berton G. Regulation of phagocyte migration and recruitment by Src-family kinases. Cell Mol Life Sci 2008;65:2175–2190.
   Google Scholar
• Courtneidge SA, Dhand R, Pilat D, Twamley GM, Waterfield MD, Roussel MF. Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor. EMBO J 1993;12:943–950.
   PubMed Web of Science ®Google Scholar
• van der Geer P, Hunter T. Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site, abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2 fibroblasts. EMBO J 1993;12:5161–5172.
   PubMed Web of Science ®Google Scholar
• Bourette RP, Arnaud S, Myles GM, Blanchet JP, Rohrschneider LR, Mouchiroud G. Mona, a novel hematopoietic-specific adaptor interacting with the macrophage colony-stimulating factor receptor, is implicated in monocyte/macrophage development. EMBO J 1998;17:7273–7281.
   PubMed Web of Science ®Google Scholar
• Bourette RP, De Sepulveda P, Arnaud S, Dubreuil P, Rottapel R, Mouchiroud G. Suppressor of cytokine signaling 1 interacts with the macrophage colony-stimulating factor receptor and negatively regulates its proliferation signal. J Biol Chem 2001;276:22133–22139.
   Google Scholar
• Garbay C, Liu WQ, Vidal M, Roques BP. Inhibitors of Ras signal transduction as antitumor agents. Biochem Pharmacol 2000;60:1165–1169.
   PubMed Web of Science ®Google Scholar
• Bourgin C, Bourette R, Mouchiroud G, Arnaud S. Expression of Mona (monocytic adapter) in myeloid progenitor cells results in increased and prolonged MAP kinase activation upon macrophage colony-stimulating factor stimulation. FEBS Lett 2000;480:113–117.
   PubMedGoogle Scholar
• Davey GM, Heath WR, Starr R. SOCS1: a potent and multifaceted regulator of cytokines and cell-mediated inflammation. Tissue Antigens 2006;67:1–9.
   PubMed Web of Science ®Google Scholar
• Chong MM, Metcalf D, Jamieson E, Alexander WS, Kay TW. Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation. Blood 2005;106:1668–1675.
   PubMed Web of Science ®Google Scholar
• Faccio R, Takeshita S, Colaianni G et al. M-CSF regulates the cytoskeleton via recruitment of a multimeric signaling complex to c-Fms Tyr-559/697/721. J Biol Chem 2007;282:18991–18999.
   PubMedGoogle Scholar
• Novak U, Nice E, Hamilton JA, Paradiso L. Requirement for Y706 of the murine (or Y708 of the human) CSF-1 receptor for STAT1 activation in response to CSF-1. Oncogene 1996;13:2607–2613.
   PubMed Web of Science ®Google Scholar
• Takeda K, Akira S. STAT family of transcription factors in cytokine-mediated biological responses. Cytokine Growth Factor Rev 2000;11:199–207.
   PubMed Web of Science ®Google Scholar
• Reedijk M, Liu X, van der Geer P et al. Tyr721 regulates specific binding of the CSF-1 receptor kinase insert to PI 3′-kinase SH2 domains: a model for SH2-mediated receptor-target interactions. EMBO J 1992;11:1365–1372.
   PubMed Web of Science ®Google Scholar
• Bourette RP, Myles GM, Choi JL, Rohrschneider LR. Sequential activation of phoshatidylinositol 3-kinase and phospholipase C-gamma2 by the M-CSF receptor is necessary for differentiation signaling. EMBO J 1997;16:5880–5893.
   PubMed Web of Science ®Google Scholar
• Coussens L, Van Beveren C, Smith D et al. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature 1986;320:277–280.
   PubMed Web of Science ®Google Scholar
• Woolford J, McAuliffe A, Rohrschneider LR. Activation of the feline c-fms proto-oncogene: multiple alterations are required to generate a fully transformed phenotype. Cell 1988;55:965–977.
   PubMed Web of Science ®Google Scholar
• Thien CB, Langdon WY. c-Cbl and Cbl-b ubiquitin ligases: substrate diversity and the negative regulation of signalling responses. Biochem J 2005;391:153–166.
   PubMed Web of Science ®Google Scholar
• Mancini A, Koch A, Wilms R, Tamura T. c-Cbl associates directly with the C-terminal tail of the receptor for the macrophage colony-stimulating factor, c-Fms, and down-modulates this receptor but not the viral oncogene v-Fms. J Biol Chem 2002;277:14635–14640.
   Google Scholar
• Wang Y, Yeung YG, Stanley ER. CSF-1 stimulated multiubiquitination of the CSF-1 receptor and of Cbl follows their tyrosine phosphorylation and association with other signaling proteins. J Cell Biochem 1999;72:119–134.
   PubMed Web of Science ®Google Scholar
• Lee PS, Wang Y, Dominguez MG et al. The Cbl protooncoprotein stimulates CSF-1 receptor multiubiquitination and endocytosis, and attenuates macrophage proliferation. EMBO J 1999;18:3616–3628.
   PubMedGoogle Scholar
• Tamura T, Mancini A, Joos H et al. FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation. Oncogene 1999;18:6488–6495.
   Google Scholar
• Mancini A, Koch A, Whetton AD, Tamura T. The M-CSF receptor substrate and interacting protein FMIP is governed in its subcellular localization by protein kinase C-mediated phosphorylation, and thereby potentiates M-CSF-mediated differentiation. Oncogene 2004;23:6581–6589.
   Google Scholar
• Boocock CA, Jones GE, Stanley ER, Pollard JW. Colony-stimulating factor-1 induces rapid behavioural responses in the mouse macrophage cell line, BAC1.2F5. J Cell Sci 1989;93 (Pt 3):447–456.
   Google Scholar
• Pixley FJ, Lee PS, Condeelis JS, Stanley ER. Protein tyrosine phosphatase phi regulates paxillin tyrosine phosphorylation and mediates colony-stimulating factor 1-induced morphological changes in macrophages. Mol Cell Biol 2001;21:1795–1809.
   PubMedGoogle Scholar
• Pixley FJ, Xiong Y, Yu RY, Sahai EA, Stanley ER, Ye BH. BCL6 suppresses RhoA activity to alter macrophage morphology and motility. J Cell Sci 2005;118:1873–1883.
   Google Scholar
• Allen WE, Jones GE, Pollard JW, Ridley AJ. Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages. J Cell Sci 1997;110:707–720.
   PubMed Web of Science ®Google Scholar
• Allen WE, Zicha D, Ridley AJ, Jones GE. A role for Cdc42 in macrophage chemotaxis. J Cell Biol 1998;141:1147–1157.
   PubMed Web of Science ®Google Scholar
• Ridley AJ. Regulation of macrophage adhesion and migration by Rho GTP-binding proteins. J Microsc 2008;231:518–523.
   Google Scholar
• Kim D, Chung J. Akt: versatile mediator of cell survival and beyond. J Biochem Mol Biol 2002;35:106–115.
   PubMedGoogle Scholar
• Kolch W. Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat Rev Mol Cell Biol 2005;6:827–837.
   PubMed Web of Science ®Google Scholar
• Chang F, Steelman LS, Lee JT et al. Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention. Leukemia 2003;17:1263–1293.
   PubMed Web of Science ®Google Scholar
• Orlofsky A, Stanley ER. CSF-1-induced gene expression in macrophages: dissociation from the mitogenic response. EMBO J 1987;6:2947–2952.
   PubMedGoogle Scholar
• Mufson RA. Induction of immediate early response genes by macrophage colony-stimulating factor in normal human monocytes. J Immunol 1990;145:2333–2339.
   Google Scholar
• Tushinski RJ, Stanley ER. The regulation of mononuclear phagocyte entry into S phase by the colony stimulating factor CSF-1. J Cell Physiol 1985;122:221–228.
   PubMed Web of Science ®Google Scholar
• Hamilton JA. CSF-1 and cell cycle control in macrophages. Mol Reprod Dev 1997;46:19–23.
   Google Scholar
• Gordon S. Alternative activation of macrophages. Nat Rev Immunol 2003;3:23–35.
   PubMed Web of Science ®Google Scholar
• Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol 2008;8:958–969.
   PubMed Web of Science ®Google Scholar
• Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat Rev Immunol 2008;8:533–544.
   PubMed Web of Science ®Google Scholar
• Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006;124:263–266.
   PubMed Web of Science ®Google Scholar
• Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141:39–51.
   PubMed Web of Science ®Google Scholar
• Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 2002;196:254–265.
   PubMed Web of Science ®Google Scholar
• Steidl C, Lee T, Shah SP et al. Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma. N Engl J Med 2010;362:875–885.
   PubMed Web of Science ®Google Scholar
• Wada N, Zaki MA, Hori Y et al. Tumour-associated macrophages in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group. Histopathology 2012;60:313–319.
   PubMed Web of Science ®Google Scholar
• Scholl SM, Pallud C, Beuvon F et al. Anti-colony-stimulating factor-1 antibody staining in primary breast adenocarcinomas correlates with marked inflammatory cell infiltrates and prognosis. J Natl Cancer Inst 1994;86:120–126.
   PubMedGoogle Scholar
• Scholl SM, Bascou CH, Mosseri V et al. Circulating levels of colony-stimulating factor 1 as a prognostic indicator in 82 patients with epithelial ovarian cancer. Br J Cancer 1994;69:342–346.
   PubMed Web of Science ®Google Scholar
• McDermott RS, Deneux L, Mosseri V et al. Circulating macrophage colony stimulating factor as a marker of tumour progression. Eur Cytokine Netw 2002;13:121–127.
   PubMed Web of Science ®Google Scholar
• Webster JA, Beck AH, Sharma M et al. Variations in stromal signatures in breast and colorectal cancer metastases. J Pathol 2010;222:158–165.
   Google Scholar
• Richardsen E, Uglehus RD, Due J, Busch C, Busund LT. The prognostic impact of M-CSF, CSF-1 receptor, CD68 and CD3 in prostatic carcinoma. Histopathology 2008;53:30–38.
   PubMed Web of Science ®Google Scholar
• Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 2001;193:727–740.
   PubMed Web of Science ®Google Scholar
• Wyckoff J, Wang W, Lin EY et al. A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 2004;64:7022–7029.
   PubMed Web of Science ®Google Scholar
• Goswami S, Sahai E, Wyckoff JB et al. Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop. Cancer Res 2005;65:5278–5283.
   PubMed Web of Science ®Google Scholar
• Roussos ET, Condeelis JS, Patsialou A. Chemotaxis in cancer. Nat Rev Cancer 2011;11:573–587.
   PubMed Web of Science ®Google Scholar
• Wang W, Wyckoff JB, Goswami S et al. Coordinated regulation of pathways for enhanced cell motility and chemotaxis is conserved in rat and mouse mammary tumors. Cancer Res 2007;67:3505–3511.
   PubMed Web of Science ®Google Scholar
• Ojalvo LS, Whittaker CA, Condeelis JS, Pollard JW. Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors. J Immunol 2010;184:702–712.
   PubMed Web of Science ®Google Scholar
• Kacinski BM. CSF-1 and its receptor in breast carcinomas and neoplasms of the female reproductive tract. Mol Reprod Dev 1997;46:71–74.
   PubMed Web of Science ®Google Scholar
• Patsialou A, Wyckoff J, Wang Y, Goswami S, Stanley ER, Condeelis JS. Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony-stimulating factor-1 receptor. Cancer Res 2009;69:9498–9506.
   PubMedGoogle Scholar
• Aharinejad S, Abraham D, Paulus P et al. Colony-stimulating factor-1 antisense treatment suppresses growth of human tumor xenografts in mice. Cancer Res 2002;62:5317–5324.
   Google Scholar
• Aharinejad S, Paulus P, Sioud M et al. Colony-stimulating factor-1 blockade by antisense oligonucleotides and small interfering RNAs suppresses growth of human mammary tumor xenografts in mice. Cancer Res 2004;64:5378–5384.
   PubMed Web of Science ®Google Scholar
• Paulus P, Stanley ER, Schäfer R, Abraham D, Aharinejad S. Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts. Cancer Res 2006;66:4349–4356.
   PubMed Web of Science ®Google Scholar
• Ahn GO, Tseng D, Liao CH, Dorie MJ, Czechowicz A, Brown JM. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci USA 2010;107:8363–8368.
   PubMed Web of Science ®Google Scholar
• Toffalini F, Demoulin JB. New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases. Blood 2010;116:2429–2437.
   PubMed Web of Science ®Google Scholar
• Reindl C, Spiekermann K. From kinases to cancer: leakiness, loss of autoinhibition and leukemia. Cell Cycle 2006;5:599–602.
   PubMed Web of Science ®Google Scholar
• Ridge SA, Worwood M, Oscier D, Jacobs A, Padua RA. FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci USA 1990;87:1377–1380.
   PubMed Web of Science ®Google Scholar
• Such E, Cervera J, Valencia A et al. Absence of mutations in the tyrosine kinase and juxtamembrane domains of C-FMS gene in chronic myelomonocytic leukemia (CMML). Leuk Res 2009;33:e162–e163.
   Google Scholar
• Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454:436–444.
   PubMed Web of Science ®Google Scholar
• Szekanecz Z, Koch AE. Macrophages and their products in rheumatoid arthritis. Curr Opin Rheumatol 2007;19:289–295.
   PubMed Web of Science ®Google Scholar
• Yang PT, Kasai H, Xiao WG et al. Increased expression of macrophage colony-stimulating factor in ankylosing spondylitis and rheumatoid arthritis. Ann Rheum Dis 2006;65:1671–1672.
   PubMedGoogle Scholar
• Bischof RJ, Zafiropoulos D, Hamilton JA, Campbell IK. Exacerbation of acute inflammatory arthritis by the colony-stimulating factors CSF-1 and granulocyte macrophage (GM)-CSF: evidence of macrophage infiltration and local proliferation. Clin Exp Immunol 2000;119:361–367.
   PubMed Web of Science ®Google Scholar
• Paniagua RT, Chang A, Mariano MM et al. c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis. Arthritis Res Ther 2010;12:R32.
   Google Scholar
• Kelley VR. Leukocyte-renal epithelial cell interactions regulate lupus nephritis. Semin Nephrol 2007;27:59–68.
   Google Scholar
• Menke J, Rabacal WA, Byrne KT et al. Circulating CSF-1 promotes monocyte and macrophage phenotypes that enhance lupus nephritis. J Am Soc Nephrol 2009;20:2581–2592.
   PubMed Web of Science ®Google Scholar
• Uemura Y, Ohno H, Ohzeki Y et al. The selective M-CSF receptor tyrosine kinase inhibitor Ki20227 suppresses experimental autoimmune encephalomyelitis. J Neuroimmunol 2008;195:73–80.
   PubMedGoogle Scholar
• Kondo Y, Duncan ID. Selective reduction in microglia density and function in the white matter of colony-stimulating factor-1-deficient mice. J Neurosci Res 2009;87:2686–2695.
   Google Scholar
• Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc Res 2008;79:360–376.
   PubMed Web of Science ®Google Scholar
• Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell 2011;145:341–355.
   PubMed Web of Science ®Google Scholar
• Clinton SK, Underwood R, Hayes L, Sherman ML, Kufe DW, Libby P. Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol 1992;140:301–316.
   PubMed Web of Science ®Google Scholar
• Rajavashisth T, Qiao JH, Tripathi S et al. Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice. J Clin Invest 1998;101:2702–2710.
   PubMed Web of Science ®Google Scholar
• Murayama T, Yokode M, Kataoka H et al. Intraperitoneal administration of anti-c-fms monoclonal antibody prevents initial events of atherogenesis but does not reduce the size of advanced lesions in apolipoprotein E-deficient mice. Circulation 1999;99:1740–1746.
   Google Scholar
• Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011;11:85–97.
   PubMed Web of Science ®Google Scholar
• Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AWJ. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003;112:1796–1808.
   PubMed Web of Science ®Google Scholar
• Xu H, Barnes GT, Yang Q et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003;112:1821–1830.
   PubMed Web of Science ®Google Scholar
• Wei S, Lightwood D, Ladyman H et al. Modulation of CSF-1-regulated post-natal development with anti-CSF-1 antibody. Immunobiology 2005;210:109–119.
   Google Scholar
• Blume-Jensen P, Hunter T. Oncogenic kinase signalling. Nature 2001;411:355–365.
   PubMed Web of Science ®Google Scholar
• Burns CJ, Wilks AF. c-FMS inhibitors: a patent review. Expert Opin Ther Pat 2011;21:147–165.
   PubMed Web of Science ®Google Scholar
• Papakonstanti EA, Zwaenepoel O, Bilancio A et al. Distinct roles of class IA PI3K isoforms in primary and immortalised macrophages. J Cell Sci 2008;121:4124–4133.
   PubMed Web of Science ®Google Scholar
• Hoellenriegel J, Meadows SA, Sivina M et al. The phosphoinositide 3′-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood 2011;118:3603–3612.
   PubMed Web of Science ®Google Scholar