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

Ana M. Santander, Omar Lopez-Ocejo, Olivia Casas, Thais Agostini, Lidia Sanchez, Eduardo Lamas-Basulto, Roberto Carrio, Margot P. Cleary, Ruben R. Gonzalez-Perez, Marta Torroella-Kouri

Research output: Contribution to journalArticle

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)143-178
Number of pages36
JournalCancers
Volume7
Issue number1
DOIs
StatePublished - Jan 15 2015

Keywords

  • Adipocytes
  • Breast adipose tissue
  • Breast cancer
  • Breast tumor cells
  • Chemotaxis
  • Diet-induced obesity
  • Inflammation
  • Macrophages
  • Obesity
  • Tumor microenvironment
  • Tumor progression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    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. (2015). 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, 7(1), 143-178. https://doi.org/10.3390/cancers7010143