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CSF-1R Signaling in Health and Disease: A Focus on the Mammary Gland

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Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Colony-stimulating factor-1 (CSF-1), also known as macrophage-colony stimulating factor (M-CSF), is the primary growth factor regulating survival, proliferation and differentiation of macrophages. It is also a potent chemokine for macrophages and monocytes. Signaling via the CSF-1 receptor (CSF-1R) is necessary for the production of almost all tissue resident macrophage populations and these macrophages participate, via trophic mechanisms, in the normal development and homeostasis of tissues and organs in which they reside, including the mammary gland. The drawback of this close interaction between macrophages and parenchymal cells is that dysregulation of macrophage trophic functions assists in the development and progression of many cancers, including breast cancer. Furthermore, tumour cells secrete CSF-1 to attract more macrophages to the tumour microenvironment where CSF-1R signaling frequently drives the behaviour of these tumour-associated macrophages (TAMs) to promote tumour progression and metastasis. Evidence is mounting that treated tumours secrete more CSF-1 and the increased recruitment of TAMs limits treatment efficacy. Thus, therapeutic targeting of the CSF-1R to inhibit TAM function is likely to enhance tumour response and improve patient outcomes in the treatment of cancer, including breast cancer.

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Abbreviations

BMM:

Bone marrow macrophage

CSF-1:

Colony-stimulating factor-1

CSF-1R:

Colony-stimulating factor-1 receptor

DCIS:

Ductal carcinoma in situ

EGF:

Epidermal growth factor

GM-CSF:

Granulocyte/macrophage-colony stimulating factor

HSC:

Hematopoietic stem cell

IL-34:

Interleukin-34

IFN:

Interferon

M-CSF:

Macrophage-colony-stimulating factor

MNP:

Mononuclear phagocyte

OP:

Osteopetrotic

PI3K:

Phosphatidylinositol 3-kinase

PIP3 :

Phosphatidylinositol 3,4,5 triphosphate

PyMT:

Polyoma middle T antigen

RANKL:

Receptor activator of nuclear factor (NF)-κB ligand

RTK:

Receptor tyrosine kinase

TAM:

Tumour-associated macrophage

TEB:

Terminal end bud

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  1. School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia

    Amy Renee Sullivan & Fiona Jane Pixley

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  1. Amy Renee Sullivan
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  2. Fiona Jane Pixley
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Correspondence to Fiona Jane Pixley.

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Sullivan, A.R., Pixley, F.J. CSF-1R Signaling in Health and Disease: A Focus on the Mammary Gland. J Mammary Gland Biol Neoplasia 19, 149–159 (2014). https://doi.org/10.1007/s10911-014-9320-1

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  • DOI: https://doi.org/10.1007/s10911-014-9320-1

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