Extracellular Vesicle-Mediated Metastasis Suppressors NME1 and NME2 Modify Lipid Metabolism in Fibroblasts

Barbara Mátyási; Gábor Petővári; Titanilla Dankó; Henriett Butz; István Likó; Péter Lőw; Isabelle Petit; Randa Bittar; Dominique Bonnefont-Rousselot; Zsolt Farkas; Tamás Szeniczey; Kinga Molnár; Krisztina Pálóczi; Edit I Buzás; Mathieu Boissan; Anna Sebestyén; Krisztina Takács-Vellai

doi:10.3390/cancers14163913

Extracellular Vesicle-Mediated Metastasis Suppressors NME1 and NME2 Modify Lipid Metabolism in Fibroblasts

Cancers (Basel). 2022 Aug 13;14(16):3913. doi: 10.3390/cancers14163913.

Authors

Barbara Mátyási¹, Gábor Petővári², Titanilla Dankó², Henriett Butz^{3

4}, István Likó³, Péter Lőw⁵, Isabelle Petit⁶, Randa Bittar^{7

8}, Dominique Bonnefont-Rousselot^{7

9}, Zsolt Farkas¹, Tamás Szeniczey¹, Kinga Molnár⁵, Krisztina Pálóczi¹⁰, Edit I Buzás^{10

11

12}, Mathieu Boissan⁶, Anna Sebestyén², Krisztina Takács-Vellai¹

Affiliations

¹ Department of Biological Anthropology, Eötvös Loránd University, 1053 Budapest, Hungary.
² Department of Pathology and Experimental Cancer Research, Semmelweis University, 1085 Budapest, Hungary.
³ Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary.
⁴ Hereditary Tumours Research Group, Hungarian Academy of Sciences, Semmelweis University, 1085 Budapest, Hungary.
⁵ Department of Anatomy, Cell and Developmental Biology, ELTE, Eötvös Loránd University, 1053 Budapest, Hungary.
⁶ Centre de Recherche Saint-Antoine, CRSA, Sorbonne Université, INSERM, 75012 Paris, France.
⁷ Service de Biochimie Métabolique, AP-HP, Sorbonne Université, Hôpitaux Universitaires Pitié-Salpêtrière-Charles Foix, 75013 Paris, France.
⁸ ICAN Maladies Cardiovasculaires et Métaboliques, Sorbonne Université, Inserm, UMR_S1166, 75013 Paris, France.
⁹ UFR de Pharmacie, Université Paris Cité, CNRS, Inserm, UTCBS, 75006 Paris, France.
¹⁰ Department of Genetics, Cell and Immunobiology, Semmelweis University, 1085 Budapest, Hungary.
¹¹ HCEMM SU Extracellular Vesicles Research Group, 1503 Budapest, Hungary.
¹² ELKH Translational Extracellular Vesicle Research Group, 1503 Budapest, Hungary.

Abstract

Nowadays, extracellular vesicles (EVs) raise a great interest as they are implicated in intercellular communication between cancer and stromal cells. Our aim was to understand how vesicular NME1 and NME2 released by breast cancer cells influence the tumour microenvironment. As a model, we used human invasive breast carcinoma cells overexpressing NME1 or NME2, and first analysed in detail the presence of both isoforms in EV subtypes by capillary Western immunoassay (WES) and immunoelectron microscopy. Data obtained by both methods showed that NME1 was present in medium-sized EVs or microvesicles, whereas NME2 was abundant in both microvesicles and small-sized EVs or exosomes. Next, human skin-derived fibroblasts were treated with NME1 or NME2 containing EVs, and subsequently mRNA expression changes in fibroblasts were examined. RNAseq results showed that the expression of fatty acid and cholesterol metabolism-related genes was decreased significantly in response to NME1 or NME2 containing EV treatment. We found that FASN (fatty acid synthase) and ACSS2 (acyl-coenzyme A synthetase short-chain family member 2), related to fatty acid synthesis and oxidation, were underexpressed in NME1/2-EV-treated fibroblasts. Our data show an emerging link between NME-containing EVs and regulation of tumour metabolism.

Keywords: NME; exosomes; extracellular vesicles; fatty acid metabolism; lipid metabolism; metastasis suppressor.

Abstract

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