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Cytokine Networks That Mediate Epithelial Cell-Macrophage Crosstalk in the Mammary Gland: Implications for Development and Cancer

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Abstract

Dynamic interactions between the hormone responsive mammary gland epithelium and surrounding stromal macrophage populations are critical for normal development and function of the mammary gland. Macrophages are versatile cells capable of diverse roles in mammary gland development and maintenance of homeostasis, and their function is highly dependent on signals within the local cytokine microenvironment. The mammary epithelium secretes a number of cytokines, including colony stimulating factor 1 (CSF1), transforming growth factor beta 1 (TGFB1), and chemokine ligand 2 (CCL2) that affect the abundance, phenotype and function of macrophages. However, aberrations in these interactions have been found to increase the risk of tumour formation, and utilisation of stromal macrophage support by tumours can increase the invasive and metastatic potential of the cancer. Studies utilising genetically modified mouse models have shed light on the significance of epithelial cell-macrophage crosstalk, and the cytokines that mediate this communication, in mammary gland development and tumourigenesis. This article reviews the current status of our understanding of the roles of epithelial cell-derived cytokines in mammary gland development and cancer, with a focus on the crosstalk between epithelial cells and the local macrophage population.

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Abbreviations

ArgI:

Arginase I

CCL2:

Chemokine ligand 2

CCR2:

C-C chemokine receptor type 2

COX2:

Cyclooxygenase 2

CSF1:

Clony stimulating factor 1

CSF1R:

Clony stimulating factor 1 receptor

DMBA:

7,12-Dimethylbenz (a) anthracene

IFNG:

Interferon gamma

IL4:

Interleukin 4

IL5:

Interleukin 5

IL12:

Interleukin 12

IL13:

Interleukin 13

iNOS:

Inducible nitric oxide synthase

LAP:

Latency-associated peptide

LTBP:

Latent TGFB binding protein

LTGFB1:

Latent transforming growth factor 1

MMTV:

Mouse mammary tumour virus

NO:

Nitric oxide

PyMT:

Polyoma middle T antigen

SOCSI:

Suppressor of cytokine signalling 1

TGFB1:

Transforming growth factor beta 1

TGFBRI:

Transforming growth factor beta type I receptor

TGFBRII:

Transforming growth factor beta type II receptor

TNFA:

Tumour necrosis factor alpha

WAP:

Whey acidic protein

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Authors and Affiliations

  1. School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia

    Xuan Sun & Wendy V. Ingman

  2. Robinson Research Institute, University of Adelaide, Adelaide, Australia

    Xuan Sun & Wendy V. Ingman

  3. Discipline of Surgery, School of Medicine, The Queen Elizabeth Hospital, University of Adelaide, Woodville, Australia

    Wendy V. Ingman

Authors
  1. Xuan Sun
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  2. Wendy V. Ingman
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Correspondence to Wendy V. Ingman.

Additional information

Funding acknowledgements: X Sun is supported by a University of Adelaide Graduate Research Scholarship and a Florey Medical Research Foundation Postgraduate Cancer Research Top Up Scholarship, WV Ingman is an NBCF/THRF Fellow.

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Sun, X., Ingman, W.V. Cytokine Networks That Mediate Epithelial Cell-Macrophage Crosstalk in the Mammary Gland: Implications for Development and Cancer. J Mammary Gland Biol Neoplasia 19, 191–201 (2014). https://doi.org/10.1007/s10911-014-9319-7

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  • DOI: https://doi.org/10.1007/s10911-014-9319-7

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