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



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.


Macrophage Cytokines TGFB CSF1 CCL2 



Arginase I


Chemokine ligand 2


C-C chemokine receptor type 2


Cyclooxygenase 2


Clony stimulating factor 1


Clony stimulating factor 1 receptor


7,12-Dimethylbenz (a) anthracene


Interferon gamma


Interleukin 4


Interleukin 5


Interleukin 12


Interleukin 13


Inducible nitric oxide synthase


Latency-associated peptide


Latent TGFB binding protein


Latent transforming growth factor 1


Mouse mammary tumour virus


Nitric oxide


Polyoma middle T antigen


Suppressor of cytokine signalling 1


Transforming growth factor beta 1


Transforming growth factor beta type I receptor


Transforming growth factor beta type II receptor


Tumour necrosis factor alpha


Whey acidic protein


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.School of Paediatrics and Reproductive HealthUniversity of AdelaideAdelaideAustralia
  2. 2.Robinson Research InstituteUniversity of AdelaideAdelaideAustralia
  3. 3.Discipline of Surgery, School of Medicine, The Queen Elizabeth HospitalUniversity of AdelaideWoodvilleAustralia

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