1. 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
- Author
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Iris Amitay-Laish, E. Hodak, C Querfeld, Lilach Moyal, Jasmine Jacob-Hirsch, B. Gorovitz‐Haris, C Arkin, Steven T. Rosen, Jamal Knaneh, and H Prag-Naveh
- Subjects
Skin Neoplasms ,Chemistry ,Cell migration ,Dermatology ,Plasma cell ,Exosomes ,Exosome ,Microvesicles ,miR-155 ,MicroRNAs ,Mycosis Fungoides ,medicine.anatomical_structure ,Real-time polymerase chain reaction ,Cell Movement ,microRNA ,Biomarkers, Tumor ,Cancer research ,medicine ,Humans ,Immunostaining - Abstract
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.
- Published
- 2021