LAUSR

Simple Summary Proteins transferred by tumor-derived exosomes can contribute to cancer progression and/or constitute novel biomarkers of a given disease. Therefore, this study used shotgun nanoLC-MS/MS to obtain complete protein profiles of four cutaneous melanoma cell lines representing different stages of the disease and exosomes released by them. As a result, 3514 and 1234 unique proteins were identified in melanoma cells and exosomes, respectively. Specific alterations to the proteomic profiles associated with disease stages have also been reported, along with a conserved portion of their proteome that may be used by various tumor cells to promote their growth and dissemination. Such a description of the complex composition of cellular and exosomal protein and their related functions provides a deeper insight into the role of exosomes in melanoma progression. The obtained results also indicate some of the exosomal proteins that should be evaluated as potential biomarkers of circulating melanoma. Abstract Intercellular transport of proteins mediated by extracellular vesicles (EVs)—exosomes and ectosomes—is one of the factors facilitating carcinogenesis. Therefore, the research on protein cargo of melanoma-derived EVs may provide a better understanding of the mechanisms involved in melanoma progression and contribute to the development of alternative biomarkers. Proteomic data on melanoma-derived EVs are very limited. The shotgun nanoLC-MS/MS approach was applied to analyze the protein composition of primary (WM115, WM793) and metastatic (WM266-4, WM1205Lu) cutaneous melanoma cells and exosomes released by them. All cells secreted homogeneous populations of exosomes that shared a characteristic set of proteins. In total, 3514 and 1234 unique proteins were identified in melanoma cells and exosomes, respectively. Gene ontology analysis showed enrichment in several cancer-related categories, including cell proliferation, migration, negative regulation of apoptosis, and angiogenesis. The obtained results broaden our knowledge on the role of selected proteins in exosome biology, as well as their functional role in the development and progression of cutaneous melanoma. The results may also inspire future studies on the clinical potential of exosomes.