Human adipose tissue macrophages display activation of cancer-related pathways

Thérèse Hérvée Mayi, Mehdi Daoudi, Bruno Derudas, Barbara Gross, Gael Bories, Kristiaan Wouters, John Brozek, Robert Caiazzo, Violeta Raverdi, Marie Pigeyre, Paola Allavena, Alberto Mantovani, François Pattou, Bart Staels, Giulia Chinetti-Gbaguidi

Research output: Contribution to journalArticlepeer-review

Abstract

Obesity is associated with a significantly increased risk for cancer suggesting that adipose tissue dysfunctions might play a crucial role therein. Macrophages play important roles in adipose tissue as well as in cancers. Here, we studied whether human adipose tissue macrophages (ATM) modulate cancer cell function. Therefore, ATM were isolated and compared with monocyte-derived macrophages (MDM) from the same obese patients. ATM, but not MDM, were found to secrete factors inducing inflammation and lipid accumulation in human T47D and HT-29 cancer cells. Gene expression profile comparison of ATM and MDM revealed overexpression of functional clusters, such as cytokine-cytokine receptor interaction (especially CXC-chemokine) signaling as well as cancer-related pathways, in ATM. Comparison with gene expression profiles of human tumor-associated macrophages showed that ATM, but not MDM resemble tumor-associated macrophages. Indirect co-culture experiments demonstrated that factors secreted by preadipocytes, but not mature adipocytes, confer an ATM-like phenotype to MDM. Finally, the concentrations of ATM-secreted factors related to cancer are elevated in serum of obese subjects. In conclusion, ATM may thus modulate the cancer cell phenotype.

Original languageEnglish
Pages (from-to)21904-21913
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number26
DOIs
Publication statusPublished - Jun 22 2012

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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