Macrophages specifically regulate the concentration of their own growth factor in the circulation.

Bartocci, A.; Mastrogiannis, Dimitrios; Migliorati, Graziella; Stockert, Richard J.; Wolkoff, Allan W.; Stanley, E. Richard

doi:10.1073/pnas.84.17.6179

Cited by 238 publications

(127 citation statements)

References 29 publications

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“…We have shown previously that blockade of CSF-1R with AFS-98 increases serum CSF-1 levels (35), most likely due to a reduction in CSF-1R-mediated CSF-1 internalization by macrophage lineage cells (47,48). Treatment of 4T1.2 and EMT6.5 tumor-bearing mice with AFS-98 significantly elevated CSF-1 levels in the serum (Fig.…”

Section: Neutralizing Anti-csf-1r Antibody and Csf-1r Inhibitors Incrmentioning

confidence: 99%

The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

Swierczak

Cook

Lenzo

et al. 2014

Cancer Immunology Research

101

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Treatment options are limited for patients with breast cancer presenting with metastatic disease. Targeting of tumor-associated macrophages through the inhibition of colony-stimulating factor-1 receptor (CSF-1R), a key macrophage signaling pathway, has been reported to reduce tumor growth and metastasis, and these treatments are now in clinical trials. Here, we report that, surprisingly, treatment with neutralizing anti-CSF-1R and anti-CSF-1 antibodies, or with two different small-molecule inhibitors of CSF-1R, could actually increase spontaneous metastasis without altering primary tumor growth in mice bearing two independently derived mammary tumors. The blockade of CSF-1R or CSF-1 led to increased levels of serum G-CSF, increased frequency of neutrophils in the primary tumor and in the metastasis-associated lung, as well as increased numbers of neutrophils and Ly6C hi monocytes in the peripheral blood. Neutralizing antibody against the G-CSF receptor, which regulates neutrophil development and function, reduced the enhanced metastasis and neutrophil numbers that resulted from CSF-1R blockade. These results indicate that the role of the CSF-1R/CSF-1 system in breast cancer is far more complex than originally proposed, and requires further investigation as a therapeutic target. Cancer Immunol Res; 2(8); 765-76. Ó2014 AACR.

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Section: Neutralizing Anti-csf-1r Antibody and Csf-1r Inhibitors Incrmentioning

confidence: 99%

The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

Swierczak

Cook

Lenzo

et al. 2014

Cancer Immunology Research

101

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“…Macrophage colony-stimulating factor (CSF-I) is a glycoprotein that is present in the circulation (10) and is required for the production of monocytes by the bone marrow and the maintenance of mature macrophage function (11). CSF-1 acts on macrophages by binding to a surface receptor (the c-fms proto-oncogene) which is a CSF-1-dependent protein tyrosine kinase (12.13).…”

Section: Abbreviations Used In This Papermentioning

confidence: 99%

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Hume¹,

Denkins

1989

Immunol Cell Biol

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Summary Bone marrow-derived murine macrophages were used to study the relationship between the proliferative response of macrophages to macrophage colony-stimulating factor (CSF-1) and their activation for cytocidal activity against tumour cells. Macrophage activation required two sequential signals. Lymphokines (gamma intcrfcron, interleukin-4) provided the first (priming) signal; bacterial products (lipopolysaccharide. lipophilic muramyl tripeptidc, Mpopeptide 31362, pertussis toxin) provided the second (triggering) signal. Both priming and triggering agents inhibited ['H]-thymidine uptakeby macrophages stimulated with CSF-1. The antiproliferative activity of priming and triggering stimuli was synergislic, Pretreatment with triggering stimuli at 37°C caused a rapid reduction of the subsequent binding of ['^^IJ-CSE-I to the cell surface at 4°C. whereas priming agents had relatively little effect. Growth inhibitionby both priming and triggering agents was largely reversible by washing the cells, and occurred even when they were added as long as 24 h after the growth factor. The ability of pertussis toxin to both inhibit CSF-1-induced proliferation and trigger cytotoxicity in macrophages suggests the involvement of a regulatory GTP-binding protein (G protein) in both processes.

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“…The spCSF-1 isoform that is increased in the serum and kidney during lupus nephritis restores renal disease (pathology and loss of function), the accumulation of intrarenal Mø, and TEC apoptosis in the MRL-Fas lpr mice deficient in CSF-1. The effect of spCSF-1 on lupus nephritis is particularly striking because spCSF-1 and sgCSF-1 have a short half-life (approximately 10 minutes) in vivo, at least in normal mice, 29 as compared with csCSF-1 (approximately 7 hours in cultured cells). 30 Moreover, our findings for the spCSF-1 isoform are even more impressive because the TgSPP/ϩ strain that we backcrossed with MRL-Fas lpr mice only generates half the amount of serum CSF-1 compared with WT mice, and the sgCSF-1 isoform is responsible for contributing the other half.…”

Section: Intrarenal Cscsf-1 and Spcsf-10 Mediate Monocyte Recruitmentmentioning

confidence: 99%

“…Saturation of the physiologic clearance mechanism greatly extends the half-life of circulating CSF-1. 29 Moreover, it is impressive that spCSF-1, as opposed to sgCSF-1, is retained in the kidney and is biologically central to advancing lupus nephritis. The ChS chain is central to the CSF-1 mechanisms advancing lupus nephritis, because the covalently-linked glycosaminoglycan ChS chain is the only difference between the precursors of the spCSF-1 and sgCSF-1.…”

Section: Intrarenal Cscsf-1 and Spcsf-10 Mediate Monocyte Recruitmentmentioning

confidence: 99%

Distinct Roles of CSF-1 Isoforms in Lupus Nephritis

Menke¹,

Iwata²,

Rabacal³

et al. 2011

Journal of the American Society of Nephrology

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Colony-stimulating factor-1 (CSF-1), the principal growth factor for macrophages, is increased in the kidney, serum, and urine of patients with lupus nephritis, and eliminating CSF-1 suppresses lupus in MRL-Fas lpr mice. CSF-1 has three biologically active isoforms: a membrane-spanning cell surface glycoprotein (csCSF-1), a secreted proteoglycan (spCSF-1), and a secreted glycoprotein (sgCSF-1); the role of each isoform in the circulation and kidney in autoimmune disease is not well understood. Here, we constructed mutant MRL-Fas lpr mice that only express csCSF-1 or precursors of the spCSF-1 and sgCSF-1 isoforms. Both csCSF-1 and spCSF-1 shifted monocytes toward proinflammatory, activated populations, enhancing their recruitment into the kidney during lupus nephritis. With advancing lupus nephritis, spCSF-1 was the predominant isoform responsible for increasing circulating CSF-1 and, along with the csCSF-1 isoform, for increasing intrarenal CSF-1. Thus, csCSF-1 appears to initiate and promote the local activation of macrophages within the kidney. Intrarenal expression of csCSF-1 and spCSF-1 increases with advancing nephritis, thereby promoting the intrarenal recruitment of monocytes and expansion of Ly6C hi macrophages, which induce apoptosis of the renal parenchyma. Taken together, these data suggest that the three CSF-1 isoforms have distinct biologic properties, suggesting that blocking both circulating and intrarenal CSF-1 may be necessary for therapeutic efficacy.

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Macrophages specifically regulate the concentration of their own growth factor in the circulation.

Cited by 238 publications

References 29 publications

The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

The Promotion of Breast Cancer Metastasis Caused by Inhibition of CSF-1R/CSF-1 Signaling Is Blocked by Targeting the G-CSF Receptor

Activation of macrophages to express cytocidal activity correlates with inhibition of their responsiveness to macrophage colony‐stimulating factor (CSF‐1): Involvement of a pertussis toxin‐sensitive reaction

Distinct Roles of CSF-1 Isoforms in Lupus Nephritis

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