title: Human adipose tissue macrophages display activation of cancer-related pathways.
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.
authors.affiliation: Université Lille Nord de France, F-59000 Lille, France.
authors.forename: Thérèse Hérvée
authors.initials: TH
authors.lastname: Mayi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Daoudi
authors.forename: Bruno
authors.initials: B
authors.lastname: Derudas
authors.forename: Barbara
authors.initials: B
authors.lastname: Gross
authors.forename: Gael
authors.initials: G
authors.lastname: Bories
authors.forename: Kristiaan
authors.initials: K
authors.lastname: Wouters
authors.forename: John
authors.initials: J
authors.lastname: Brozek
authors.forename: Robert
authors.initials: R
authors.lastname: Caiazzo
authors.forename: Violeta
authors.initials: V
authors.lastname: Raverdi
authors.forename: Marie
authors.initials: M
authors.lastname: Pigeyre
authors.forename: Paola
authors.initials: P
authors.lastname: Allavena
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Giulia
authors.initials: G
authors.lastname: Chinetti-Gbaguidi
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000273:Adipose Tissue / Q000378:metabolism*; D001391:Azo Compounds / Q000494:pharmacology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype
chemical_list: D001391:Azo Compounds; D018925:Chemokines; C011049:oil red O