title: Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer.
abstract: Malignant progression results from a dynamic cross-talk between stromal and cancer cells. Recent evidence suggests that this cross-talk is mediated to a significant extent by exosomes, nanovesicles secreted by most cell types and which allow the transfer of proteins, lipids, and nucleic acids between cells. Adipocytes are a major component of several tumor microenvironments, including that of invasive melanoma, where cells have migrated to the adipocyte-rich hypodermic layer of the skin. We show that adipocytes secrete exosomes in abundance, which are then taken up by tumor cells, leading to increased migration and invasion. Using mass spectrometry, we analyzed the proteome of adipocyte exosomes. Interestingly, these vesicles carry proteins implicated in fatty acid oxidation (FAO), a feature highly specific to adipocyte exosomes. We further show that, in the presence of adipocyte exosomes, FAO is increased in melanoma cells. Inhibition of this metabolic pathway completely abrogates the exosome-mediated increase in migration. Moreover, in obese mice and humans, both the number of exosomes secreted by adipocytes as well as their effect on FAO-dependent cell migration are amplified. These observations might in part explain why obese melanoma patients have a poorer prognosis than their nonobese counterparts. Cancer Res; 76(14); 4051-7. ©2016 AACR.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Ikrame
authors.initials: I
authors.lastname: Lazar
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Emily
authors.initials: E
authors.lastname: Clement
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dauvillier
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Milhas
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Manuelle
authors.initials: M
authors.lastname: Ducoux-Petit
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, INSERM U1048, UPS, Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: LeGonidec
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, INSERM U1048, UPS, Toulouse, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Moro
authors.affiliation: Plateforme de Microscopie Electronique Intégrative, CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Soldan
authors.affiliation: Centre de recherche en Cancérologie de Lyon, Université Lyon 1, Pierre Bénite, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dalle
authors.affiliation: Plateforme de Microscopie Electronique Intégrative, CNRS, Université de Toulouse, Toulouse, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Balor
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Muriel
authors.initials: M
authors.lastname: Golzio
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Burlet-Schiltz
authors.affiliation: Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, INSERM U1048, UPS, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Muller
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France. Laurence.Nieto@ipbs.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Nieto
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D002465:Cell Movement; D055354:Exosomes / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications*; D010084:Oxidation-Reduction
chemical_list: D005227:Fatty Acids