Extracellular vesicles and melanoma: New perspectives on tumor microenvironment and metastasis

Abstract

Secreted extracellular vesicles (EVs) are lipid bilayer particles without functional nucleus naturally released from cells which constitute an intercellular communication system. There is a broad spectrum of vesicles shed by cells based on their physical properties such as size (small EVs and large EVs), biogenesis, cargo and functions, which provide an increasingly heterogenous landscape. In addition, they are involved in multiple physiological and pathological processes. In cancer, EV release is opted by tumor cells as a beneficial process for tumor progression. Cutaneous melanoma is a cancer that originates from the melanocyte lineage and shows a favorable prognosis at early stages. However, when melanoma cells acquire invasive capacity, it constitutes the most aggressive and deadly skin cancer. In this context, extracellular vesicles have been shown their relevance in facilitating melanoma progression through the modulation of the microenvironment and metastatic spreading. In agreement with the melanosome secretory capacity of melanocytes, melanoma cells display an enhanced EV shedding activity that has contributed to the utility of melanoma models for unravelling EV cargo and functions within a cancer scenario. In this review, we provide an in-depth overview of the characteristics of melanoma-derived EVs and their role in melanoma progression highlighting key advances and remaining open questions in the field.

Melanocytes in regenerative medicine applications and disease modeling

“…They have been shown to contain miR-211, miR-155 and miR-210 that target the MAPK pathway and aerobic glycolysis, and decrease oxidative phosphorylation in fibroblasts [ 186 , 187 ]. A pro-inflammatory role of EVs derived from CM cells has been observed compared to normal melanocytes (reviewed in [ 188 ]).…”

“…They have been shown to contain miR-211, miR-155 and miR-210 that target the MAPK pathway and aerobic glycolysis, and decrease oxidative phosphorylation in fibroblasts [186,187]. A pro-inflammatory role of EVs derived from CM cells has been observed compared to normal melanocytes (reviewed in [188]). UM cells secrete EVs that reach the liver and induce the release of cytokines and growth factors in hepatic cells, such as macrophage inhibitory factor (MIF), which in turn promotes the recruitment of melanoma cells to the liver in a murine model [189].…”

CD63/81 Small Extracellular Vesicles in the Aqueous Humor are Retinoblastoma Associated

“…Small EVs are the most well described in the setting of cancer 27 and are also the predominant size found in intraocular biofluids. 31 – 35 For cancer, tumor-derived sEVs have been shown to promote tumor formation, progression, treatment resistance, and metastases 24 , 36 , 37 allowing for the discovery of diagnostic and prognostic biomarkers for multiple cancer types, including breast, 38 lung, 39 , 40 gastric, 36 and melanoma, 41 among others. 24 In the eyes, sEVs have been investigated in diseases including age-related macular degeneration, retinal vascular disease, glaucoma, uveitis, and thyroid eye disease, primarily through analysis of tissue, cell lines, and serum, whereas AH studies are limited.…”