Primary Melanoma miRNA Trafficking Induces Lymphangiogenesis

Gil S. Leichner, Inbal Schweitzer, Shani Dror, Lotan Levin, Polina Geva, Tamar Golan, Laureen Zaremba, Guy Shapira, Roma Parikh, Noam Shomron, Aviv Barzilai, Jörg D. Hoheisel, Carmit Levy, Shoshana Greenberger

Research output: Contribution to journalArticlepeer-review


Melanoma, the deadliest cutaneous tumor, initiates within the epidermis; during progression, cells invade into the dermis and become metastatic through the lymphatic and blood system. Before melanoma cell invasion into the dermis, an increased density of dermal lymphatic vessels is observed, generated by a mechanism which is not fully understood. In this study, we show that, while at the primary epidermal stage (in situ), melanoma cells secrete extracellular vesicles termed melanosomes, which are uptaken by dermal lymphatic cells, leading to transcriptional and phenotypic pro-lymphangiogenic changes. Mechanistically, melanoma-derived melanosomes traffic mature let-7i to lymphatic endothelial cells, which mediate pro-lymphangiogenic phenotypic changes by the induction of type I IFN signaling. Furthermore, transcriptome analysis upon treatment with melanosomes or let-7i reveals the enhancement of IFI6 expression in lymphatic cells. Because melanoma cells metastasize primarily via lymphatic vessels, our data suggest that blocking lymphangiogenesis by repressing either melanosome release or type I IFN signaling will prevent melanoma progression to the deadly metastatic stage.

Original languageEnglish
Pages (from-to)1788-1798.e7
JournalJournal of Investigative Dermatology
Issue number9
StatePublished - Sep 2023

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


Dive into the research topics of 'Primary Melanoma miRNA Trafficking Induces Lymphangiogenesis'. Together they form a unique fingerprint.

Cite this