The Role of Extracellular Vesicles in Melanoma Progression

SIMPLE SUMMARY: Melanoma is produced by the malignant transformation of the pigmented cells in the skin. It is the deadliest form of skin cancer and a global medical burden. Recent research suggests that extracellular vesicles improve diagnosis and treatment of melanoma. Extracellular vesicles are virus-like vehicles that are released into the blood and other body fluids by most cell types, including cancer cells. They sequester molecular substances from the cytoplasm and transport them as messengers to target cells. Thanks to these properties, extracellular vesicles provide a molecular fingerprint of the cell of origin and can serve as biomarkers for cancer diagnosis or prognosis. In addition, molecular signals exchanged through extracellular vesicles between cancer cells and the tumor environment can reveal signaling pathways that are important for cancer progression. In this review we give a general overview of extracellular vesicles and focus on their impact on melanoma progression and potential use as biomarkers for monitoring and treating melanoma. ABSTRACT: Cutaneous melanoma arises from a malignant transformation of the melanocytes in the skin. It is the deadliest form of skin cancer owing to its potential to metastasize. While recent advances in immuno-oncology have been successful in melanoma treatment, not all the patients respond to the treatment equally, thus individual pre-screening and personalized combination therapies are essential to stratify and monitor patients. Extracellular vesicles (EVs) have emerged as promising biomarker candidates to tackle these challenges. EVs are ~50–1000-nm-sized, lipid bilayer-enclosed spheres, which are secreted by almost all cell types, including cancer cells. Their cargo, such as nucleic acids, proteins, lipids, amino acids, and metabolites, can be transferred to target cells. Thanks to these properties, EVs can both provide a multiplexed molecular fingerprint of the cell of origin and thus serve as potential biomarkers, or reveal pathways important for cancer progression that can be targeted pharmaceutically. In this review we give a general overview of EVs and focus on their impact on melanoma progression. In particular, we shed light on the role of EVs in shaping the tumor–stroma interactions that facilitate metastasis and summarize the latest findings on molecular profiling of EV-derived miRNAs and proteins that can serve as potential biomarkers for melanoma progression.