GSE211556
Extracellular Vesicle-Mediated Metastasis Suppressors NME1  and NME2 Modify Lipid Metabolism in Fibroblasts
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 capillaryWestern 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. Overall design: Transcriptomic analysis of patient-derived normal fibroblasts treated by NME1-EVs, NME2-EVs compared to control vector containing Evs (Co-EVs) derived from MDA-MB-231T triple negative breast carcinoma cells.