Mycosis fungoides‐derived exosomes promote cell motility and are enriched with microRNA‐155 and microRNA‐1246, and their plasma‐cell‐free expression may serve as a potential biomarker for disease burden

Summary Background Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking. Objectives To characterize MF‐derived exosomes and their involvement in the disease. Methods Exosomes were isolated by ultracentrifugation from cutaneous T‐cell lymphoma (CTCL) cell lines, and from plasma of patients with MF and controls (healthy individuals). Exosomes were confirmed by electron microscopy, NanoSight and CD81 staining. Cell‐line exosomes were profiled for microRNA array. Exosomal microRNA (exomiRNA) expression and uptake, and plasma‐cell‐free microRNA (cfmiRNA) were analysed by reverse‐transcriptase quantitative polymerase chain reaction. Exosome uptake was monitored by fluorescent labelling and CD81 immunostaining. Migration was analysed by transwell migration assay. Results MyLa‐ and MJ‐derived exosomes had a distinctive microRNA signature with abundant microRNA (miR)‐155 and miR‐1246. Both microRNAs were delivered into target cells, but only exomiR‐155 was tested, demonstrating a migratory effect on target cells. Plasma levels of cfmiR‐1246 were significantly highest in combined plaque/tumour MF, followed by patch MF, and were lowest in controls (plaque/tumour > patch > healthy), while cfmiR‐155 was upregulated only in plaque/tumour MF vs. controls. Specifically, exomiR‐1246 (and not exomiR‐155) was higher in plasma of plaque/tumour MF than in healthy controls. Plasma exosomes from MF but not from controls increased cell migration. Conclusions Our findings show that MF‐derived exosomes promote cell motility and are enriched with miR‐155, a well‐known microRNA in MF, and miR‐1246, not previously reported in MF. Based on their plasma expression we suggest that they may serve as potential biomarkers for tumour burden. What is already known about this topic? Cancer‐derived exosomes mediate tumour progression by delivering microRNAs such as miR‐155 and miR‐1246 into recipient cells, and their cell‐free (cf) components are upregulated in plasma of patients with cancer. What does this study add? Mycosis fungoides (MF) cell‐line exosomes carry miR‐155 and miR‐1246, deliver them to recipient cells (malignant and benign), and increase their migration through miR‐155. cfmiR‐1246, cfmiR‐155 and exosomal miR‐1246 are upregulated in plasma of patients with MF, mainly in tumour/plaque‐stage disease. What is the translational message? Extracellular miR‐155 and miR‐1246 may serve as targets for novel t