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Tumor Discovery Melanoma exosomes in metastasis

exclusion chromatography, often fail to distinguish miRNAs are enriched in melanoma-derived exosomes,
these subpopulations, resulting in heterogeneous where they modulate various aspects of tumor biology. 41,42
preparations. Asymmetric-flow field-flow fractionation For instance, miR-211 is associated with the promotion
and immunoaffinity-based separation techniques offer of melanoma cell invasion, while miR-155 is involved in
43
improved resolution, preserving vesicle integrity and immune modulation. The transfer of these miRNAs to
specificity. Recognizing exosome heterogeneity and recipient cells can alter their behavior, contributing to the
optimizing isolation methods are crucial for advancing metastatic process. 44,45
biomarker discovery and therapeutic applications. The
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endosomal sorting complexes required for transport 3.1.2. Long non-coding RNAs
(ESCRT) complex operates in a stepwise manner, with Long non-coding RNAs are non-coding RNA molecules
ESCRT-0 identifying ubiquitinated cargo, ESCRT-I and longer than 200 nucleotides that influence gene activity
ESCRT-II facilitating membrane curvature, and ESCRT- through transcriptional, post-transcriptional, and
III completing vesicle separation. 30-32 These MVBs follow epigenetic mechanisms. In melanoma, certain lncRNAs are
two possible pathways: they can merge with lysosomes, selectively packaged into exosomes, where they contribute
41
leading to their breakdown, or be directed to the plasma to tumor progression. For example, lncRNA metastasis-
membrane, where their contents are discharged into the associated lung adenocarcinoma transcript 1 plays a
surrounding extracellular environment as exosomes. significant role in driving melanoma cell growth and
33
46
The direction of MVB trafficking is influenced by Rab facilitating their migratory behavior. Moreover, studies
GTPases, such as Rab27a and Rab27b, which facilitate reveal that metastasis-associated lung adenocarcinoma
34
MVB docking and fusion with the plasma membrane, transcript 1 supports melanoma growth and metastasis by
thus promoting exosome release. The biogenesis process activating critical oncogenic pathways.
35
is orchestrated by multiple proteins, such as tetraspanins 3.1.3. Circular RNAs (circRNAs)
36
(cluster of differentiation [CD] 63, CD81, and CD9),
which are essential for cargo sorting and exosome release. circRNAs are a class of non-coding RNAs characterized
The ESCRT machinery is also integral to the formation by their unique covalently bonded circular configuration.
30
of exosomes. 37 They act as competitive endogenous RNAs, sequestering
miRNAs and influencing the expression of downstream
The molecular composition of melanoma-derived genes. In melanoma, circRNA cerebellar degeneration-
exosomes is significantly distinct from that of exosomes related protein 1 (PD-1) antisense RNA has been identified
secreted by normal cells, as they contain specific proteins, as a competitive binder of miR-7-5p, which, in turn,
lipids, and nucleic acids that contribute to tumor progression, stabilizes and upregulates oncogenes like E2F transcription
immune modulation, and metastasis. Tumor-derived factor 3. This interaction promotes tumor cell
47
exosomes are enriched in proteins associated with tumor proliferation, invasion, and altered glucose metabolism. 48
progression, such as matrix metalloproteinases (MMPs),
integrins, and various oncogenic signaling molecules. 3.2. DNA
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In addition, they contain a unique profile of miRNAs Exosomal DNA (exoDNA), derived from the cell’s nucleus
that can modulate gene expression in recipient cells, and mitochondria, plays a crucial role in melanoma
influencing processes such as proliferation, invasion, and progression and metastasis. Sorting mechanisms and
immune evasion. Key examples include miR-211, which interactions with endosomal components are involved in
39
35
downregulates the tumor suppressor brain-2 to promote its packaging. 50,51
invasion, and miR-155, which suppresses immune cell
40
activation by targeting the suppressor of cytokine signaling 1. Studies have shown that tumor-derived exoDNA
contains oncogenic mutations, which can be transferred
3. Exosomal cargo in melanoma to recipient cells, influencing TME remodeling, immune
escape, and drug resistance. In addition, exoDNA serves
The cargo of exosomes derived from melanoma cells as a biomarker for liquid biopsy, offering non-invasive
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provides a rich source of information about the tumor’s diagnostic potential for melanoma. 49,53
molecular landscape.
3.3. Proteins
3.1. RNA
Tumor-derived exosomes carry key regulatory proteins,
3.1.1. miRNAs
including MMPs, which degrade the ECM to promote
miRNAs are small RNA molecules that regulate gene tumor invasion and migration. 30,54 In addition, exosomes
expression at the post-transcriptional level. Specific transport signaling molecules such as integrins and growth

Volume 4 Issue 2 (2025) 6 doi: 10.36922/td.7108