Mycosis fungoides-derived exosomes promote cell motility, are enriched with miR-155 and miR-1246, and their plasma cell-free expression may serve as potential biomarkers for disease burden.
Literature regarding exosomes as mediators in intercellular communication to promote progression in mycosis fungoides (MF) is lacking.To characterize MF-derived exosomes and their involvement in the disease.Exosomes were isolated by ultracentrifugation from cutaneous T-cell lymphoma (CTCL) cell lines, plasma of MF patients, and controls (healthy individuals), and confirmed by electron microscopy, NanoSight, and CD81 staining. Cell-line exosomes were profiled for miRNA array. Exosomal miRNA (exomiR) expression, uptake and plasma cell-free miRNA (cfmiRNA) were analyzed by RT-qPCR. Exosome uptake was monitored by fluorescent labeling and CD81 immunostaining. Migration was analyzed by transwell migration assay.MyLa and MJ-derived exosomes had a distinctive miRNA signature with abundant miR-155 and miR-1246. Both miRs were delivered into target cells, but only exomiR-155 was tested and demonstrated a migratory effect on target cells. Plasma levels of cfmiR-1246 were significantly highest in plaque/tumor MF, followed by patch MF and lowest in controls (plaque/tumor>patch>healthy), while cfmiR-155 was only upregulated in plaque/tumor MF vs controls. Specifically, exomiR-1246 (and not exomiR-155) was higher in plasma of plaque/tumor MF vs healthy. Plasma exosomes from MF but not controls increased cell migration.Our findings showed that MF-derived exosomes promote cell motility and are enriched with miR-155, a well-known miR 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 tumor burden.
Authors: L Moyal, C Arkin, B Gorovitz-Haris, C Querfeld, S Rosen, J Knaneh, I Amitay-Laish, H Prag-Naveh, J Jacob-Hirsch, E Hodak