Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration

Bland, Cassidy L.; Byrne-Hoffman, Christina N.; Fernández, Audry; Rellick, Stephanie L.; Deng, Wentao; Klinke, David J.

doi:10.1111/febs.14396

Cited by 64 publications

(49 citation statements)

References 43 publications

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“…For instance, tumors secrete growth factor-, mRNA- and miRNA-containing micro-vesicles, which can be found in the blood of cancer patients and are important players in the metastatic process (reviewed in [ 47 ]). Along this line, a recent study reported that exosomes derived from B16-F10 cells are positive for mRNA and miRNA molecules, which affect the epigenetic landscape and mitochondrial respiration in cytotoxic T cells [ 75 ]. Classical effects of TMaE are related to cancer-associated cachexia, systemic inflammation, immune system suppression, and altered coagulation [ 47 , 48 ].…”

Section: Resultsmentioning

confidence: 99%

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

Assis

Moraes

Magalhães-Marques

et al. 2018

IJMS

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The biological clock has received increasing interest due to its key role in regulating body homeostasis in a time-dependent manner. Cancer development and progression has been linked to a disrupted molecular clock; however, in melanoma, the role of the biological clock is largely unknown. We investigated the effects of the tumor on its micro- (TME) and macro-environments (TMaE) in a non-metastatic melanoma model. C57BL/6J mice were inoculated with murine B16-F10 melanoma cells and 2 weeks later the animals were euthanized every 6 h during 24 h. The presence of a localized tumor significantly impaired the biological clock of tumor-adjacent skin and affected the oscillatory expression of genes involved in light- and thermo-reception, proliferation, melanogenesis, and DNA repair. The expression of tumor molecular clock was significantly reduced compared to healthy skin but still displayed an oscillatory profile. We were able to cluster the affected genes using a human database and distinguish between primary melanoma and healthy skin. The molecular clocks of lungs and liver (common sites of metastasis), and the suprachiasmatic nucleus (SCN) were significantly affected by tumor presence, leading to chronodisruption in each organ. Taken altogether, the presence of non-metastatic melanoma significantly impairs the organism’s biological clocks. We suggest that the clock alterations found in TME and TMaE could impact development, progression, and metastasis of melanoma; thus, making the molecular clock an interesting pharmacological target.

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Section: Resultsmentioning

confidence: 99%

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

Assis

Moraes

Magalhães-Marques

et al. 2018

IJMS

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“…We hypothesize that greater transcriptome changes in embryos treated with oEVs could be found if embryos were analyzed after a shorter period of IVC, for example after a few hours. Bland et al [42] observed changes in the T-cell transcriptome after as little as 0.5 h of exosome treatment, while other transcriptome changes were observed after 8 h of treatment. This study suggested that exosome treatment elicits a dynamic transcriptomic signature in cytotoxic T cells that becomes apparent for some clusters of genes at 0.5 h, while others needed a longer treatment period.…”

Section: Oviductal Evs Regulate Early Embryonic Development By Alterimentioning

confidence: 99%

The Oviductal Extracellular Vesicles’ RNA Cargo Regulates the Bovine Embryonic Transcriptome

Bauersachs

Mermillod

Almiñana

2020

IJMS

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Oviductal extracellular vesicles (oEVs) are emerging as key players in the gamete/embryo–oviduct interactions that contribute to successful pregnancy. Various positive effects of oEVs on gametes and early embryos have been found in vitro. To determine whether these effects are associated with changes of embryonic gene expression, the transcriptomes of embryos supplemented with bovine fresh (FeEVs) or frozen (FoEVs) oEVs during in vitro culture compared to controls without oEVs were analyzed by low-input RNA sequencing. Analysis of RNA-seq data revealed 221 differentially expressed genes (DEGs) between FoEV treatment and control, 67 DEGs for FeEV and FoEV treatments, and minor differences between FeEV treatment and control (28 DEGs). An integrative analysis of mRNAs and miRNAs contained in oEVs obtained in a previous study with embryonic mRNA alterations pointed to direct effects of oEV cargo on embryos (1) by increasing the concentration of delivered transcripts; (2) by translating delivered mRNAs to proteins that regulate embryonic gene expression; and (3) by oEV-derived miRNAs which downregulate embryonic mRNAs or modify gene expression in other ways. Our study provided the first high-throughput analysis of the embryonic transcriptome regulated by oEVs, increasing our knowledge on the impact of oEVs on the embryo and revealing the oEV RNA components that potentially regulate embryonic development.

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“…Moreover, Bland et al have recently discovered an alternative mechanism of melanoma derived-Exo, which affect the epigenetic landscape and mitochondrial respiration of cytotoxic T-cells. This results in their reduced activation [34]. Studies in different types of cancer also demonstrate that tumor-derived EVs restrain the expansion and differentiation of myeloid-derived suppressor cells (MDSCs) and T-regulatory cells (Treg) [35,36] as well as reduce the cytotoxic activity of natural killer (NK) cells by down-regulating NKG2D, NKp30, NKP46, and NKG2C receptors [37].…”

Section: Role Of Exo In Melanoma Progressionmentioning

confidence: 99%

Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression

Mannavola

D’Oronzo

Cives

et al. 2019

IJMS

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Cutaneous melanoma shows a high metastatic potential based on its ability to overcome the immune system’s control. The mechanisms activated for these functions vary extremely and are also represented by the production of a number of extracellular vesicles including exosomes. Other vesicles showing a potential role in the melanoma progression include oncosomes and melanosomes and the majority of them mediate tumor processes including angiogenesis, immune regulation, and modifications of the micro-environment. Moreover, a number of epigenetic modifications have been described in melanoma and abundant production of altered microRNAs (mi-RNAs), non-coding RNAs, histones, and abnormal DNA methylation have been associated with different phases of melanoma progression. In addition, exosomes, miRNAs, and other molecular factors have been used as potential biomarkers reflecting disease evolution while others have been suggested to be potential druggable molecules for therapeutic application.

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Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration

Abstract: Gene expression data are available in the GEO database under the accession SuperSeries number GSE102951.

Cited by 64 publications

References 43 publications

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

Non-Metastatic Cutaneous Melanoma Induces Chronodisruption in Central and Peripheral Circadian Clocks

The Oviductal Extracellular Vesicles’ RNA Cargo Regulates the Bovine Embryonic Transcriptome

Extracellular Vesicles and Epigenetic Modifications Are Hallmarks of Melanoma Progression

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