1213 Exosome-mediated RNAi delivery for melanoma therapy

Abstract

Reflectance confocal microscopy (RCM) allows the identification of four malignant melanoma (MM) subtypes: dendritic-cell (DC), round cell (RN), dermal-nest (DN) and combinedtype (CT). The aim was to study the biomolecular profile of MM RCM-subtypes. 85 MM were evaluated by RCM and characterized by clinical, dermoscopic and histopatological analyses. DC and RC melanoma were generally Radial Growth Phase in stage I and II, while CT and DN were Vertical Growth Phase in stage III and IV. Ki67, as shown by immunohistochemistry, was significantly more expressed in the epidermis of DC and RC. CD271 expression increased from DC to RC and decreased from RC to CT. This correlates with our previously published concept that CD271 has a switch on-off function in melanoma progression. ABCB5 expression was lower in RC than in DC, CT and DN. Co-expression of BMF and BRAFv660E was observed in CT, while it inversely correlated in DC, RC and DN. Nestin and Sox2 were highly co-expressed in CT and DN, indicating a more aggressive behaviour of CT and DN, as compared to DC. RNAs extracted from paraffin-embedded melanoma tissues were analysed for the expression of 770 genes by NanoString technology. The analysis revealed significant differences in the expression of genes involved in chemotaxis, inflammation, cell-cell adhesion, cell motility and angiogenesis. While CT melanomas were able to generate spheroids, DC did not form a compact spheroid, probably because of its less proliferative capacity, as shown by MTT assay. Collagen invasion assay confirmed that DC is a less aggressive tumour, as compared to the other RCM-subtypes. These results represent a first step to develop a new method to diagnose and manage melanoma, reaching a more accurate patient/tumour tailored therapeutic approach.