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Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment
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Cancers 2015, 7(1), 143-178; doi:10.3390/cancers7010143

Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue

1
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA
2
Hormel Institute, University of Minnesota, Austin, MN 55912, USA
3
Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA 30314, USA
4
Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, 1475 NW 12th Ave, Miami, FL 33136, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Reto Schwendener
Received: 8 October 2014 / Accepted: 5 January 2015 / Published: 15 January 2015
(This article belongs to the Special Issue Tumor Associated Macrophages)
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Abstract

The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity. View Full-Text
Keywords: breast cancer; obesity; breast adipose tissue; inflammation; tumor microenvironment; macrophages; adipocytes; breast tumor cells; chemotaxis; diet-induced obesity; tumor progression breast cancer; obesity; breast adipose tissue; inflammation; tumor microenvironment; macrophages; adipocytes; breast tumor cells; chemotaxis; diet-induced obesity; tumor progression
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Santander, A.M.; Lopez-Ocejo, O.; Casas, O.; Agostini, T.; Sanchez, L.; Lamas-Basulto, E.; Carrio, R.; Cleary, M.P.; Gonzalez-Perez, R.R.; Torroella-Kouri, M. Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue. Cancers 2015, 7, 143-178.

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