1202 Melanoma–derived melanosomes induce lymphangiogenesis through miRNAs trafficking

Melanoma is the most aggressive and treatment-resistant of all human skin cancers and is responsible for approximately 80% of skin cancer mortalities. Melanoma, initiates within the epidermis; during progression, cells invade into the dermis and become primary metastatic through the blood vessels and lymphatic system. First develop metastatic growth occurs by spreading to their draining lymphatic nodes via lymphatic vessels, but the mechanism is not fully understood. In current study we found, that at stage 0 melanoma (in-situ), melanoma-derived extract cellular vesicles, termed melanosomes up taken by dermal lymphatic cells, alerting pro-lymphangiogenic phenotype such us endothelial cell proliferation, migration, in vitro tube formation and spheroid sprouting. More specifically, melanosome traffic mature let-7i to lymphatic endothelial cells which mediate pro-lymphangiogenic transcriptional and phenotypic changes by the induction of Type I Interferon signaling. Further analysis of transcriptome revealed upregulating of IFI6 in lymphatic cells. Our findings offer a promising opportunity to block melanoma cell metastasis by preventing the formation of the dermal lymphatic vessels via targeting tumor-stroma communications.