title: Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion.
abstract: Early local tumor invasion in breast cancer results in a likely encounter between cancer cells and mature adipocytes, but the role of these fat cells in tumor progression remains unclear. We show that murine and human tumor cells cocultivated with mature adipocytes exhibit increased invasive capacities in vitro and in vivo, using an original two-dimensional coculture system. Likewise, adipocytes cultivated with cancer cells also exhibit an altered phenotype in terms of delipidation and decreased adipocyte markers associated with the occurrence of an activated state characterized by overexpression of proteases, including matrix metalloproteinase-11, and proinflammatory cytokines [interleukin (IL)-6, IL-1β]. In the case of IL-6, we show that it plays a key role in the acquired proinvasive effect by tumor cells. Equally important, we confirm the presence of these modified adipocytes in human breast tumors by immunohistochemistry and quantitative PCR. Interestingly, the tumors of larger size and/or with lymph nodes involvement exhibit the higher levels of IL-6 in tumor surrounding adipocytes. Collectively, all our data provide in vitro and in vivo evidence that (i) invasive cancer cells dramatically impact surrounding adipocytes; (ii) peritumoral adipocytes exhibit a modified phenotype and specific biological features sufficient to be named cancer-associated adipocytes (CAA); and (iii) CAAs modify the cancer cell characteristics/phenotype leading to a more aggressive behavior. Our results strongly support the innovative concept that adipocytes participate in a highly complex vicious cycle orchestrated by cancer cells to promote tumor progression that might be amplified in obese patients.
authors: Université de Toulouse, Toulouse, France.
authors: Béatrice
authors: B
authors: Dirat
authors: Ludivine
authors: L
authors: Bochet
authors: Marta
authors: M
authors: Dabek
authors: Danièle
authors: D
authors: Daviaud
authors: Stéphanie
authors: S
authors: Dauvillier
authors: Bilal
authors: B
authors: Majed
authors: Yuan Yuan
authors: YY
authors: Wang
authors: Aline
authors: A
authors: Meulle
authors: Bernard
authors: B
authors: Salles
authors: Sophie
authors: S
authors: Le Gonidec
authors: Ignacio
authors: I
authors: Garrido
authors: Ghislaine
authors: G
authors: Escourrou
authors: Philippe
authors: P
authors: Valet
authors: Catherine
authors: C
authors: Muller
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000473:pathology*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010641:Phenotype
chemical_list: D015850:Interleukin-6