Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Second-Hand Melanoma Melanosomes Regulate Diversity Among Tumor-Associated Macrophages

ABSTRACT: Extracellular vesicles (EVs) are a key form of cell-to-cell communication. Here we reveal a new mode of communication involving the large EVs, melanosomes. Unlike small EVs, which are dissolved in the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell, a state we term “second-hand EVs”. We found that melanoma-secreted melanosomes uptaken by and then released from epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. The respective consequence for macrophages is polarization into pro-tumor or pro-immune-cell-infiltration phenotypes. Fibroblasts load melanosomes with AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in-vivo. In melanoma patients, macrophages co-localized with AKT1, were correlated with disease aggressiveness, and immunotherapy non-responders were enriched in macrophages containing melanosome markers. Thus, the network of interactions via second-hand EVs helps form the metastatic niche. Since macrophage heterogeneity is pivotal in advancement of cancer, our data suggest an opportunity to halt melanoma progression by blocking the melanosome cues of macrophage diversification.

ORGANISM(S): Homo sapiens

PROVIDER: GSE246446 | GEO | 2023/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Second-Hand Melanoma Melanosomes Regulate Diversity Among Tumor-Associated Macrophages

Project description:Extracellular vesicles (EVs) are a key form of cell-to-cell communication. Here we reveal a new mode of communication involving the large EVs, melanosomes. Unlike small EVsexosomes, which are dissolved in the receiver cell, melanosomes stay intact within them, gain a unique protein signature, and can then be further transferred to another cell, a state we term “second-hand EVs”. We found that melanoma-secreted melanosomes uptaken by and then released from epidermal keratinocytes or dermal fibroblasts can be further engulfed by resident macrophages. The respective consequence for macrophages is polarization into pro-tumor or pro-immune-cell-infiltration phenotypes. Fibroblasts load melanosomes with AKT1, which induces VEGF secretion from macrophages in an mTOR-dependent manner, promoting angiogenesis and metastasis in-vivo. In melanoma patients, macrophages co-localized with AKT1, were correlated with disease aggressiveness, and immunotherapy non-responders were enriched in macrophages containing melanosome markers. Thus, the network of interactions via second-hand EVs helps form the metastatic niche. Since macrophage heterogeneity is pivotal in advancement of cancer, our data suggest an opportunity to halt melanoma progression by blocking the melanosome cues of macrophage diversification.

2023-12-31 | PXD046421 | Pride

Second-Hand Melanoma Melanosomes Regulate Diversity Among Tumor-Associated Macrophages

Project description:Second-Hand Melanoma Melanosomes Regulate Diversity Among Tumor-Associated Macrophages

| PRJNA1032944 | ENA

Expression profiling of fibroblasts treated with miR-211 and miR-320c

Project description:mRNA profiles generated from primary fibroblast upon treatment with miR-211, miR-302 or melanoma melanosomes. Abstract: Melanoma originates in the epidermis and enters the metastatic and lethal phase upon invasion into the dermis. However, the interactions between melanoma cells and the dermis prior to this invasion have been poorly studied. Here we uncover that melanoma cells directly affect the formation of the dermal tumor niche by microRNA (miRNA) trafficking prior to invading the dermis. Melanocytes, the cells of melanoma origin, are specialized in trafficking of pigment vesicles, termed melanosomes and, interestingly, melanoma cells retain this trafficking ability. In melanoma in-situ specimens, we found melanosome markers in distal fibroblasts prior to the invasion of melanoma cells into the dermis. Melanoma-derived melanosomes carry miRNAs into primary fibroblasts that trigger changes in the fibroblasts, including increased proliferation, migration, and expression of pro-inflammatory genes, all known features of cancer-associated fibroblasts (CAFs). Specifically, we found that melanosomal miRNA-211 directly targets IGF2R and leads to MAPK signaling activation in fibroblasts, which reciprocally encourages melanoma growth. Treatment of melanoma cells with a melanosome release-inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest a promising opportunity to block melanoma cell invasion by preventing the formation of the dermal tumor niche. In the paper we showed the 10% of most differentially expressed mRNA upon miR-211, miR-320c and melanosomes treatment and overlap of 2000 downregulated mRNA upon miR-211 and melanosomes treatment with predicted target gene miR-211 and CAFs related genes Expresssion profiling was performed for primary fibroblasts transfected with miRNA-211 mimic and miRNA-320c mimic.

2016-08-09 | E-GEOD-72619 | biostudies-arrayexpress

Analysis of melanosomal miRNAs

Project description:miRNA microarray profiling was performed for MNT-1 cells, pre-mature and mature melanosomes extracted from MNT-1 cells. In order to reveal the miRNAs that are most abundant in mature melanosomes, the most highly expressed miRNAs from mature melanosomes were compared with expression levels in pre-mature melanosomes. The analysis revealed five miRNAs that were highly expressed in mature melanosomes and had been previously associated with melanoma. Total RNA was extracted from MNT-1 cells (2 replicates), pre-mature and mature melanosomes. The melanosomes were either treated with RNase prior to RNA extraction (2 replicates each) or untreated (1 replicate each). Melanosomes were extracted from MNT-1 melanoma cells by sucrose-based density gradient ultracentrifugation. The treatment of melanosomes with RNase prior to RNA extraction was performed in order to remove any kind of RNA that may interact with or stick unspecifically to the outer side of the melanosome membrane. After 10 mins of RNAse treatment, RNase inhibitor was added. The samples of MNT-1 cells and untreated melanosomes were considered for the normalization, but not for further analyses. Microarray Unit of the Core Facility Genomics and Proteomics DKFZ

2016-08-09 | E-GEOD-72337 | biostudies-arrayexpress

Expression profiling of fibroblasts treated with miR-211 and miR-320c

2016-08-09 | GSE72619 | GEO

Analysis of melanosomal, exosomal and cellular miRNAs of melanoma cells

Project description:miRNA microarray profiling was performed for exosomes and secreted melanosomes of MNT-1 cells as well as WM3682 and WM3314 cells and melanosomes isolated from cell homogenates. The aim of this study is to compare the miRNA content of exosomes and secreted melanosomes and to assess differences in the miRNA profiles of different melanoma cell lines and their melanosomes. Total RNA was extracted from MNT-1 exosomes and secreted melanosomes (2 replicates each) that were isolated from the conditioned medium of MNT-1 melanoma cells by differential ultracentrifugation. In addition, total RNA was isolated from WM3682 and WM3314 melanoma cells and melanosomes (1 replicate each). These latter melanosomes were isolated from cell homogenates by filtration through a 0.45 Âµm filter, followed by FACS sorting. Contributor: Microarray Unit of the Core Facility Genomics and Proteomics DKFZ

2016-08-09 | E-GEOD-79411 | biostudies-arrayexpress

Expression profiling of fibroblasts treated with melanosomes

Project description:mRNA profiling was performed on primary fibroblasts treated with melanosomes and untreated fibroblasts as control. The aim of this study was to explore whether melanoma-derived mature melanosomes functionally affect primary fibroblasts. A functional gene set enrichment analysis based on the resulting mRNA profiles predicted that an uptake of mature melanosomes by fibroblasts causes increased cell proliferation and cell motility. Expression profiling was performed for 3 replicates of primary human fibroblasts that were treated with mature melanosomes, 1 replicate of fibroblasts treated with early melanosomes and 3 replicates of untreated fibroblasts as controls. Melanosomes were extracted from the human melanoma cell line MNT-1. Fibroblasts were treated with melanosomes for 24h. Fold changes were calculed for fibroblasts treated with mature melanosomes vs. controls. The sample of fibroblasts treated with early melanosomes was considered for the normalization, but not for further analyses. Microarray Unit of the Core Facility Genomics and Proteomics DKFZ

2016-08-09 | E-GEOD-72229 | biostudies-arrayexpress

Analysis of melanosomal, exosomal and cellular miRNAs of melanoma cells

2016-08-09 | GSE79411 | GEO

Analysis of melanosomal miRNAs

2016-08-09 | GSE72337 | GEO

Distinct non-coding RNA cargo of extracellular vesicles from M1 and M2 human primary macrophages

Project description:Purpose: Macrophages are often classified into M1 ‘classical’ and M2 ‘alternatively-activated’ macrophages. Extracellular vesicles (EVs) are biomolecule carriers involved in cell-cell communication. Here, we provide a first insight into the complete small RNA cargo of human macrophage M1/M2 EVs. Methods: Monocyte-derived macrophages were polarised into M1 (GM-CSF+LPS+IFNγ) or M2 (M-CSF+IL-4+IL-13) and EVs isolated by size exclusion chromatography. EVs were characterised by nanoparticle tracking analysis, electron microscopy and ELISA. EV RNA samples were prepared for small RNA sequencing using Qiagen’s GIAseq small RNA Library Prep kit and sequenced on an Illumina NextSeq500, single end 75 bp. Functional enrichment analysis was performed using MIENTURNET, based on validated miR-target interactions from miRTarBase. Results: Many types of small non-coding RNAs were found in EVs from M1/M2 macrophages including miRNAs, isomiRs, tRNA fragments, piRNA, snRNA, snoRNA and yRNA fragments. Distinct differences were observed between M1 and M2 EVs, with higher relative abundance of miRNAs, and lower abundance of tRNA fragments in M1 EVs compared to M2 EVs. MicroRNA-target enrichment analysis identified several gene targets involved in gene expression and metabolic processes. Conclusions: M1 and M2 cells release EVs with distinct tRNA and miRNA cargo, which have the potential to contribute to the unique effect of these cell subsets on their microenvironment.

2022-12-07 | GSE207286 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data