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Cancer Res. 2016 Jul 15;76(14):4051-7. doi: 10.1158/0008-5472.CAN-16-0651. Epub 2016 May 23.

Adipocyte Exosomes Promote Melanoma Aggressiveness through Fatty Acid Oxidation: A Novel Mechanism Linking Obesity and Cancer.

Author information

1
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France.
2
Institut des Maladies Métaboliques et Cardiovasculaires, Université de Toulouse, INSERM U1048, UPS, Toulouse, France.
3
Plateforme de Microscopie Electronique Intégrative, CNRS, Université de Toulouse, Toulouse, France.
4
Centre de recherche en Cancérologie de Lyon, Université Lyon 1, Pierre Bénite, France.
5
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, Toulouse, France. Laurence.Nieto@ipbs.fr.

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.

PMID:
27216185
DOI:
10.1158/0008-5472.CAN-16-0651
[Indexed for MEDLINE]
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