Analysis of the miRNA Profiles of Melanoma Exosomes Derived Under Normoxic and Hypoxic Culture Conditions

Wozniak, Michal; Pęczek, Łukasz; Czernek, Liliana; Duechler, Markus

doi:10.21873/anticanres.12138

Cited by 24 publications

(27 citation statements)

References 45 publications

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“…Our findings about the molecular cargo of sEVs are in accordance with previous studies, which also showed changes in the exosomal content upon exposure of the donor cells to external stimuli and stress conditions 41,44,47,48 . Furthermore, Peinado et al 17 and Lazar et al 49 , analysing protein composition of different melanoma cell line-derived exosomes, also found melanocyte-specific proteins, transmembrane proteins, such as tetraspanins, transporters and receptors as well as MVB and endosomal pathway-related proteins, for instance ESCRT-associated proteins, annexins, cytoskeletal and small GTP-binding proteins 17,49 . comprehensive in silico analysis of functional differences between sEV groups.…”

Section: Encapsulation Of Ag-tio 2 Nanoparticles Into Sevs Cannot Be supporting

confidence: 92%

“…These areas have a special chemical microenvironment with low oxygen, low pH and low nutrient concentration. Intrinsic stress conditions, such as hypoxia and acidosis increase exosome release from malignant cells and lead to TME alteration and expansion, which subsequently results in tumour progression 48,49 .…”

Section: Role Of Intrinsic Microenvironmental Factors In the Exosome-mentioning

confidence: 99%

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Small extracellular vesicles convey the stress response of tumour cells

Harmati

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Exosomes are small extracellular vesicles (sEVs), playing a crucial role in the intercellular communication in physiological as well as pathological processes. Here, we aimed to study whether the melanoma-derived seV-mediated communication could adapt to microenvironmental stresses. We compared B16F1 cell-derived sEVs released under normal and stress conditions, including cytostatic, heat and oxidative stress. The miRNome and proteome showed substantial differences across the sEV groups and bioinformatics analysis of the obtained data by the Ingenuity Pathway Analysis also revealed significant functional differences. The in silico predicted functional alterations of seVs were validated by in vitro assays. For instance, melanoma-derived sEVs elicited by oxidative stress increased Ki-67 expression of mesenchymal stem cells (MSCs); cytostatic stress-resulted sEVs facilitated melanoma cell migration; all sEV groups supported microtissue generation of MSC-B16F1 co-cultures in a 3D tumour matrix model. Based on this study, we concluded that (i) molecular patterns of tumourderived sEVs, dictated by the microenvironmental conditions, resulted in specific response patterns in the recipient cells; (ii) in silico analyses could be useful tools to predict different stress responses; (iii) alteration of the seV-mediated communication of tumour cells might be a therapy-induced host response, with a potential influence on treatment efficacy. Exosomes are small (30-200 nm) 1 endosome-derived vesicles that are actively secreted into the extracellular environment from most cell types. Initially, exosomes were proposed to eliminate cellular waste, but it has been proven that they also play a key role in the intercellular communication between adjacent as well as distal cells through the horizontal transfer of lipids, proteins and nucleic acids. Over the past three decades, exosomes have surged to the forefront of cell biology research, and recently an increasing body of evidence indicates that this exosomal communication is a deliberate and highly orchestrated process. Clinical relevance of exosomes is also considerable, since they are associated with numerous physiological and pathological conditions, including cancer diseases 2 .

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Section: Encapsulation Of Ag-tio 2 Nanoparticles Into Sevs Cannot Be supporting

confidence: 92%

Section: Role Of Intrinsic Microenvironmental Factors In the Exosome-mentioning

confidence: 99%

Small extracellular vesicles convey the stress response of tumour cells

Harmati

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“…Micro RNA profiles of TEX differ from miRNA profiles of their donor cancer cells as well as from profiles of sEV released by normal cells [ 78 , 79 , 80 , 81 ]. The majority of available works report miRNA signatures of pure MTEX released in vitro by melanoma cell lines [ 69 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ]. Moreover, a few studies addressed miRNA composition of sEV derived from serum/plasma of melanoma patients [ 82 , 91 , 92 , 93 , 94 ].…”

Section: The Molecular Cargo Of Mtexmentioning

confidence: 99%

“…Similar to proteomics data, few consistencies were observed among these studies due to different models applied. Nevertheless, there were 6 MTEX-upregulated miRNA species reported in more than one study: miR-494 [ 82 , 83 ], let-7c [ 69 , 84 ], miR-690 [ 84 , 85 ], miR-17 [ 84 , 91 ], and miR-494 [ 82 , 83 ], while miR-125b was reported to be downregulated in MTEX or sEV from plasma of melanoma patients [ 83 , 92 ]. Noteworthy, all the above mentioned miRs are known to be involved in cancer cell invasion, migration, and proliferation as well as in inflammatory processes linked to tumorigenesis and cancer progression [ 82 , 83 , 84 , 85 , 86 , 91 , 92 ].…”

Section: The Molecular Cargo Of Mtexmentioning

confidence: 99%

Signaling of Tumor-Derived sEV Impacts Melanoma Progression

Zebrowska

Widłak

Whiteside

et al. 2020

IJMS

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Small extracellular vesicles (sEV or exosomes) are nanovesicles (30–150 nm) released both in vivo and in vitro by most cell types. Tumor cells produce sEV called TEX and disperse them throughout all body fluids. TEX contain a cargo of proteins, lipids, and RNA that is similar but not identical to that of the “parent” producer cell (i.e., the cargo of exosomes released by melanoma cells is similar but not identical to exosomes released by melanocytes), possibly due to selective endosomal packaging. TEX and their role in cancer biology have been intensively investigated largely due to the possibility that TEX might serve as key component of a “liquid tumor biopsy.” TEX are also involved in the crosstalk between cancer and immune cells and play a key role in the suppression of anti-tumor immune responses, thus contributing to the tumor progression. Most of the available information about the TEX molecular composition and functions has been gained using sEV isolated from supernatants of cancer cell lines. However, newer data linking plasma levels of TEX with cancer progression have focused attention on TEX in the patients’ peripheral circulation as potential biomarkers of cancer diagnosis, development, activity, and response to therapy. Here, we consider the molecular cargo and functions of TEX as potential biomarkers of one of the most fatal malignancies—melanoma. Studies of TEX in plasma of patients with melanoma offer the possibility of an in-depth understanding of the melanoma biology and response to immune therapies. This review features melanoma cell-derived exosomes (MTEX) with special emphasis on exosome-mediated signaling between melanoma cells and the host immune system.

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“…Hypoxic conditions promote the invasive potential of malignant melanocytes [ 92 ] and increase the amount of specific miRNAs in exosomes (e.g., miR-494, miR-513a, miR-4497, miR-6087) [ 93 , 94 ]. Hypoxia-inducible factor 1 alpha (HIF1α), key player in the cellular response to oxygen deprivation [ 95 ], promotes the expression of several miRNAs (miR-210, miR-218, miR-224, and miR-452) that contribute to tumour cell plasticity and aggressiveness, by targeting and increasing BNIP3 (BCL2/adenovirus E1B interacting protein 3), associated with glutamine metabolism [ 96 , 97 , 98 ].…”

Section: Non-coding Rnas and The Interplay With The Melanoma Micromentioning

confidence: 99%

The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy

Lazăr

Dinescu

Costache

2020

Cancers

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Considered to be highly lethal if not diagnosed in early stages, cutaneous malignant melanoma is among the most aggressive and treatment-resistant human cancers, and its incidence continues to rise, largely due to ultraviolet radiation exposure, which is the main carcinogenic factor. Over the years, researchers have started to unveil the molecular mechanisms by which malignant melanoma can be triggered and sustained, in order to establish specific, reliable biomarkers that could aid the prognosis and diagnosis of this fatal disease, and serve as targets for development of novel efficient therapies. The high mutational burden and heterogeneous nature of melanoma shifted the main focus from the genetic landscape to epigenetic and epitranscriptomic modifications, aiming at elucidating the role of non-coding RNA molecules in the fine tuning of melanoma progression. Here we review the contribution of microRNAs and lncRNAs to melanoma invasion, metastasis and acquired drug resistance, highlighting their potential for clinical applications as biomarkers and therapeutic targets.

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Analysis of the miRNA Profiles of Melanoma Exosomes Derived Under Normoxic and Hypoxic Culture Conditions

Abstract: The miRNA-expression profiles of exosomes from patient-derived melanoma cells are modified by oxygen concentration and reflect the phenotypic changes of melanoma cells under different growth conditions.

Cited by 24 publications

References 45 publications

Small extracellular vesicles convey the stress response of tumour cells

Small extracellular vesicles convey the stress response of tumour cells

Signaling of Tumor-Derived sEV Impacts Melanoma Progression

The Non-Coding Landscape of Cutaneous Malignant Melanoma: A Possible Route to Efficient Targeted Therapy

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