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Tumor Discovery Melanoma exosomes in metastasis

factors, which facilitate pre-metastatic niche formation and 4.2. Shaping the TME
immune modulation. 55,56 Tumor-derived exosomes also Melanoma-derived exosomes are crucial in remodeling the
contain proteins involved in drug resistance, which modulate surrounding tumor ecosystem. By transferring bioactive
therapy responses by altering signaling pathways. 21 molecules to stromal cells, these exosomes can alter the
Melanoma-derived exosomes contain a diverse set behavior of the surrounding cells, creating a favorable
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of proteins that participate in key signaling pathways environment for tumor growth and metastasis. For
associated with metastasis. For example, proteins such as instance, exosomes can stimulate fibroblasts to produce
MMPs facilitate ECM degradation, allowing for tumor pro-inflammatory cytokines, leading to increased
invasion and migration. 57,58 Furthermore, exosomal angiogenesis and enhanced nutrient supply for the tumor.
lipids can modulate signaling networks and influence the Moreover, exosomes can modify the ECM, making it more
activities of recipient cells, further enhancing metastatic conducive to tumor invasion. 65
potential. 33
4.3. EMT
3.4. Lipids A key process driven by melanoma-derived exosomes
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Exosomal lipids play a significant role in melanoma is EMT, a biological mechanism that enables epithelial
progression by influencing membrane stability, intracellular cells to acquire migratory and invasive characteristics.
signaling, and metabolic adaptation. Lipid rafts in Exosomal miRNAs, such as miR-211, can downregulate
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exosomes serve as platforms for signal transduction, while E-cadherin, a key adhesion molecule, promoting EMT and
6
specific lipids, such as sphingolipids and ceramides, are enhancing the invasive capacity of melanoma cells. This
involved in cell communication and apoptosis regulation. transition not only aids in local invasion but also prepares
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Dysregulated lipid content in melanoma-derived exosomes melanoma cells for dissemination to distant organs. 26
has been associated with enhanced metastatic potential 4.4. Immune evasion
and immune evasion. 61
Melanoma cells exploit exosomes to evade the immune
3.5. Other biomolecules in exosomes system. Exosomes can modulate the function of immune
Beyond nucleic acids, proteins, and lipids, melanoma- cells, including dendritic cells and T-cells, promoting a
derived exosomes also contain small metabolites that tolerogenic environment. For instance, melanoma-derived
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influence tumor metabolism and interactions with the exosomes can carry PD-L1, which binds to programmed
microenvironment. These metabolites include amino cell death PD-1 receptors on T-cells, leading to T-cell
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acids, sugars, and vitamins, which support tumor inhibition. This immune suppression allows melanoma
proliferation and modulate immune responses. Glycolytic cells to escape detection and destruction, thereby
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intermediates found in tumor exosomes contribute to facilitating their survival and proliferation.
metabolic reprogramming, while vitamins and cofactors 4.5. Pre-metastatic niche formation
regulate oxidative stress and mitochondrial function.
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Understanding the metabolic landscape of melanoma- Exosomes also contribute to the formation of pre-
derived exosomes could provide novel therapeutic targets metastatic niches, which are sites in distant organs that
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for disrupting tumor-supportive pathways. 39 are primed for the arrival and growth of metastatic cells.
Melanoma-derived exosomes can induce changes in the
4. Contribution of melanoma-derived microenvironment of these distant sites, such as the lungs
exosomes to metastasis or liver, by promoting inflammation and altering the local
cellular composition. This pre-conditioning enhances
Exosomes derived from melanoma cells play a multifaceted the likelihood of successful colonization by circulating
role in promoting metastasis through various mechanisms: melanoma cells. 69

4.1. Promotion of tumor growth 4.6. Biomarkers and therapeutic targets
Exosomes can carry and deliver oncogenic factors, Given their role in metastasis, melanoma-derived
such as growth molecules, including growth regulators exosomes are being explored as potential biomarkers for
and cytokines, to neighboring cells, thereby promoting disease progression and therapeutic targets. The unique
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tumor growth and invasion. For example, melanoma- molecular signatures of these exosomes can provide
derived exosomes contain vascular endothelial growth insights into tumor dynamics and patient prognosis.
factor, which promotes angiogenesis and enhances tumor Furthermore, targeting exosomal pathways – whether by
vascularization. 63 inhibiting their release, blocking their uptake, or altering

Volume 4 Issue 2 (2025) 7 doi: 10.36922/td.7108