The Influence of Melanoma Extracellular Vesicles on Benign Melanocytes: A Role for PRAME in Modulation of the Tumor Microenvironment

Abstract

Melanoma is an aggressive skin cancer with a high tendency for metastasis and resistance to conventional therapies. This study explores the role of preferentially expressed antigen in melanoma (PRAME), a cancer-testis antigen, in melanoma progression, focusing on its function in melanoma-derived extracellular vesicles (EVs) and its impact on benign melanocytes. We show that PRAME is highly expressed in melanoma cell lines, tissues, and patient plasma and is present in EVs. These EVs transfer PRAME protein and mRNA to benign melanocytes, leading to significant alterations in gene expression, increased cell proliferation, and a more malignant phenotype. Knockout of PRAME in melanoma cells reduces these protumorigenic effects on melanocytes, emphasizing PRAME’s role in EV-mediated communication. The detection of PRAME in plasma EVs suggests its potential as a biomarker for monitoring disease progression and therapy response, including in rare melanoma subtypes. These findings highlight PRAME as a key player in melanoma progression and suggest targeting PRAME-containing EVs as a potential therapeutic strategy to inhibit melanoma progression and metastasis.