CSF-1 regulation of the wandering macrophage: complexity in action

Pixley, Fiona J.; Stanley, E. Richard

doi:10.1016/j.tcb.2004.09.016

Cited by 689 publications

(716 citation statements)

References 91 publications

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“…Chemokines and chemokine receptors have been used as targets for the development of therapeutic strategies to control inflammatory disorders, and recent results suggest that chemokine inhibitors also affect tumour growth by reducing macrophage infiltration (Balkwill, 2004). Colony stimulating factor 1 (CSF-1), a cytokine commonly produced by tumours, triggers monocyte migration (Pixley and Stanley, 2004) and blocking CSF-1 or its receptor has been shown to suppress macrophage infiltration and to reduce tumour growth (Aharinejad et al, 2004). Recently, it was shown by Allavena et al (2005) that Yondelis (Trabectedin), a new anticancer agent of marine origin, markedly reduced the levels of proinflammatory cytokines CCL2 and IL-6 in monocytes and macrophages, thus inhibiting macrophage viability, differentiation and cytokine production.…”

Section: Discussionmentioning

confidence: 99%

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

et al. 2006

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Tumour-associated macrophages, TAMs, play a pivotal role in tumour growth and metastasis by promoting tumour angiogenesis. Treatment with clodronate encapsulated in liposomes (clodrolip) efficiently depleted these phagocytic cells in the murine F9 teratocarcinoma and human A673 rhabdomyosarcoma mouse tumour models resulting in significant inhibition of tumour growth ranging from 75 to 492%, depending on therapy and schedule. Tumour inhibition was accompanied by a drastic reduction in blood vessel density in the tumour tissue. Vascular endothelial growth factor (VEGF) is one of the major inducers of tumour angiogenesis and is also required for macrophage recruitment. The strongest effects were observed with the combination therapy of clodrolip and a VEGF-neutralising antibody, whereas free clodronate was not significantly active. Immunohistologic evaluation of the tumours showed significant depletion of F4/80 þ and MOMA-1 þ and a less pronounced depletion of CD11b þ TAMs. Blood vessel staining (CD31) and quantification of the vessels as well as TAMs and tumour-associated dendritic cells (TADCs) in the A673 model showed reduction rates of 85 to 494%, even 9 days after the end of therapy. In addition, CD11c þ TADCs, which have been shown to potentially differentiate into endothelial-like cells upon stimulation by tumour released growth and differentiation factors, were similarly reduced by clodrolip or antibody treatment. These results validate clodrolip therapy in combination with angiogenesis inhibitors as a promising novel strategy for an indirect cancer therapy aimed at the haematopoietic precursor cells that stimulate tumour growth and dissemination and as a tool to study the role of macrophages and dendritic cells in tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

et al. 2006

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“…In the macrophage/osteoclast lineage, a homodimeric cytokine, CSF-1, is the primary regulator of survival, proliferation, and differentiation (reviewed in Ref. 22). Major events triggered by engagement of the CSF-1 receptor, c-Fms, include activation of STAT1, STAT3, the MAPK, and the PI3K/AKT pathways (23)(24)(25)(26).…”

Section: Bcl-6 Negatively Regulatesmentioning

confidence: 99%

BCL-6 Negatively Regulates Expression of the NF-κB1 p105/p50 Subunit

Wang

et al. 2005

The Journal of Immunology

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BCL-6 is a transcription repressor frequently deregulated in non-Hodgkin’s B cell lymphomas. Its activity is also critical to germinal center development and balanced Th1/Th2 differentiation. Previous studies have suggested that NF-κB activity is suppressed in germinal center and lymphoma B cells that express high levels of BCL-6, and yet the reason for this is unknown. We report in this study that BCL-6 can bind to three sequence motifs in the 5′ regulatory region of NF-κB1 in vitro and in vivo, and repress NF-κB1 transcription both in reporter assays and in lymphoma B cell lines. BCL-6−/− mice further confirm the biological relevance of BCL-6-dependent regulation of NF-κB1 because BCL-6 inactivation caused notable increase in p105/p50 proteins in several cell types. Among these, BCL-6−/− macrophage cell lines displayed a hyperproliferation phenotype that can be reversed by NF-κB inhibitors, e.g., N-tosyl-l-phenylalanine chloromethyl ketone and SN50, a result that is consistent with increased nuclear κB-binding activity of p50 homodimer and p50/p65 heterodimer. Our results demonstrate that BCL-6 can negatively regulate NF-κB1 expression, thereby inhibiting NF-κB-mediated cellular functions.

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“…Tumorassociated macrophages (TAM), which have been subjected to extensive study, can execute several key roles required for tumor growth and progression (1,2). Colony-stimulating factor-1 (CSF-1/M-CSF) regulates the recruitment, differentiation, survival, and proliferation of macrophages (3). CSF-1 activity is mediated through its interaction with the receptor tyrosine kinase, CSF-1 receptor (CSF-1R/c-Fms/CD115; ref.…”

Section: Introductionmentioning

confidence: 99%

“…CSF-1 activity is mediated through its interaction with the receptor tyrosine kinase, CSF-1 receptor (CSF-1R/c-Fms/CD115; ref. 3), which is expressed primarily on mononuclear phagocytic cells and their precursors (4). Interleukin-34 (IL34) is a second ligand for CSF-1R; it controls the development of specific macrophage lineages, such as microglia and Langerhans cells (5).…”

Section: Introductionmentioning

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

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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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CSF-1 regulation of the wandering macrophage: complexity in action

Cited by 689 publications

References 91 publications

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach

BCL-6 Negatively Regulates Expression of the NF-κB1 p105/p50 Subunit

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

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