Breast-Associated Adipocytes Secretome Induce Fatty Acid Uptake and Invasiveness in Breast Cancer Cells via CD36 Independently of Body Mass Index, Menopausal Status and Mammary Density
by
Maurice Zaoui 1,†, Mehdi Morel 1,†, Nathalie Ferrand 1, Soraya Fellahi 2, Jean-Philippe Bastard 2, Antonin Lamazière 3, Annette Kragh Larsen 1, Véronique Béréziat 4,‡
, Michael Atlan 5,‡ and Michèle Sabbah 1,*
Maurice Zaoui 1,†, Mehdi Morel 1,†, Nathalie Ferrand 1, Soraya Fellahi 2, Jean-Philippe Bastard 2, Antonin Lamazière 3, Annette Kragh Larsen 1, Véronique Béréziat 4,‡, Michael Atlan 5,‡ and Michèle Sabbah 1,*
1
Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UMR_S 938, Centre de Recherche Saint-Antoine, Team Cancer Biology and Therapeutics, Institut Universitaire de Cancérologie, Sorbonne Université, F-75012 Paris, France
2
Department of Biochemistry and Hormonology, Tenon Hospital, AP-HP, F-75020 Paris, France
3
Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UMR 70203, Laboratory of Biomolecules, École Normale Supérieure, AP-HP, F-75012 Paris, France
4
Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), UMR_S 938, Centre de Recherche Saint-Antoine, Team Genetic and Acquired Lipodystrophies, Institut Hospitalo-Universitaire de Cardiométabolisme et Nutrition, Sorbonne Université, F-75012 Paris, France
5
Department of Plastic Surgery, Reconstructive, Aesthetic, Microsurgery and Tissue Regeneration, Tenon Hospital, Institut Universitaire de Cancérologie, AP-HP, F-75020 Paris, France
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors share equal senior authorship.
Cancers 2019, 11(12), 2012; https://doi.org/10.3390/cancers11122012
Received: 8 October 2019 / Revised: 29 November 2019 / Accepted: 10 December 2019 / Published: 13 December 2019
Breast adiposity is correlated with body mass index, menopausal status and mammary density. We here wish to establish how these factors influence the cross-talk between breast adipocytes and normal or malignant breast cells. Adipocyte-derived stem cells (ASCs) were obtained from healthy women and classified into six distinct groups based on body mass index, menopausal status and mammary density. The ASCs were induced to differentiate, and the influence of their conditioned media (ACM) was determined. Unexpectedly, there were no detectable differences in adipogenic differentiation and secretion between the six ASC groups, while their corresponding ACMs had no detectable influence on normal breast cells. In clear contrast, all ACMs profoundly influenced the proliferation, migration and invasiveness of malignant breast cells and increased the number of lipid droplets in their cytoplasm via increased expression of the fatty acid receptor CD36, thereby increasing fatty acid uptake. Importantly, inhibition of CD36 reduced lipid droplet accumulation and attenuated the migration and invasion of the breast cancer cells. These findings suggest that breast-associated adipocytes potentiate the invasiveness of breast cancer cells which, at least in part, is mediated by metabolic reprogramming via CD36-mediated fatty acid uptake.
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Keywords:
breast cancer; adiposity; body mass index; menopausal status; mammary density; fatty acid; CD36
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MDPI and ACS Style
Zaoui, M.; Morel, M.; Ferrand, N.; Fellahi, S.; Bastard, J.-P.; Lamazière, A.; Larsen, A.K.; Béréziat, V.; Atlan, M.; Sabbah, M. Breast-Associated Adipocytes Secretome Induce Fatty Acid Uptake and Invasiveness in Breast Cancer Cells via CD36 Independently of Body Mass Index, Menopausal Status and Mammary Density. Cancers 2019, 11, 2012.
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