Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ECM deposition is driven by caveolin1-dependent regulation of exosomal biogenesis and cargo sorting

ABSTRACT:

The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism.

Linked studies: MTBLS1977

INSTRUMENT(S): Liquid Chromatography MS - Negative (LC-MS (Negative))

SUBMITTER: JesÃºs Balsinde

PROVIDER: MTBLS1969 | MetaboLights | 2020-10-07

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Similar Datasets

ECM deposition is driven by caveolin1-dependent regulation of exosomal biogenesis and cargo sorting

Project description:The composition and physical properties of the extracellular matrix (ECM) critically influence tumor progression, but the molecular mechanisms underlying ECM layering are poorly understood. Tumor-stroma interaction is critically dependent on cell-cell communication mediated by exosomes, small vesicles generated within multivesicular bodies (MVBs). Here, we show that caveolin-1 (Cav1) is a central modulator of both exosome biogenesis and exosomal protein cargo sorting through the regulation of cholesterol content at the endosomal compartment/MVBs. Quantitative proteomics profiling revealed that Cav1 is required for exosomal sorting of ECM protein cargo subsets including tenascin-C (TnC), and for fibroblast-derived exosomes to efficiently depose ECM and promote tumor cell invasiveness. Cav1-driven exosomal ECM deposition not only promotes local stromal remodeling, but also the generation of distant ECM-enriched stromal niches. These results support a model by which Cav1 is a central regulatory hub for tumor-stroma interactions through a novel exosome-dependent ECM deposition mechanism. Linked studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS1969' rel='noopener noreferrer' target='_blank'>MTBLS1969</a>

2020-10-07 | MTBLS1977 | MetaboLights

Identification of a Cxcl10+ monocyte subset with a pathogenic signature in the CNS during auto-immune neuroinflammation

Project description:Multiple Sclerosis (MS) is characterized by pathological inflammation resulting from recruitment of lymphoid and myeloid immune cells from the blood circulation into the central nervous system (CNS). Due to cellular heterogeneity, defining the functional roles of these subsets in acute and chronic stages of MS has been challenging. Here we used index sorting and transcriptional single-cell sequencing to characterize peripheral mononuclear phagocyte infiltrates in the MS mouse model, experimental autoimmune encephalomyelitis (EAE). Based on their transcriptomes, we identified eight monocyte and three dendritic cell subsets during disease pathology with defined characteristics pointing towards distinct functions. Cell ablation identified two specific monocytic subsets with a pathogenic potential. Congenic monocyte transfer experiments combined with indexed-lineage sorting coupled to scRNA-seq established that these pathogenic cells are not descendants of the canonical Ly6C+ monocytes but derived from early myeloid cell progenitors. These results suggest a potential for targeted therapeutic interventions aimed at blocking specific pathogenic monocytic subsets.

2020-04-20 | GSE144317 | GEO

Ral GTPases promote metastasis by controlling biogenesis and organotropism of exosomes

Project description:Cancer extracellular vesicles (EVs) mainly exert pro-tumoral functions by changing the phenotypes of stromal cells to the benefit of tumor growth and metastasis. In particular, they shuttle to distant organs and seed pre-metastatic niches facilitating subsequent colonization by circulating tumor cells. The levels of tumor secreted EVs have been correlated to tumor aggressiveness, however, the link between EV secretion mechanisms, their capacity to form pre-metastatic niches and the actual formation of metastasis remains obscure. Here, we show that two GTPases RalA and RalB control, through the phospholipase PLD1, the homeostasis of multi-vesicular bodies and thereby tune the biogenesis and secretion of a subtype of (pro-metastatic) EVs. Mice experiments revealed that RalA and RalB promote lung metastasis of mammary carcinoma cells without affecting their invasive behaviors. Importantly, we show in vivo that EVs from RalA or RalB depleted cells have limited organotropic capacities and, as a consequence, are less efficient in priming lung metastasis. Furthermore, we show that such EVs lack the adhesion molecule MCAM/CD146, which is responsible for EVs organotropism. Finally, we show that RalA and RalB have increased expression in human breast cancer patients with lung metastasis. Altogether, our study identifies Ral GTPases as central molecules linking the mechanisms of EVs secretion, cargo loading to their capacity to disseminate and induce pre-metastatic niches.

2021-09-09 | PXD020180 | Pride

RNA sequencing data of CNS-associated macrophages (CAMs) isolated from brains of Mrc1-CreERT2 mice

Project description:All tissue resident macrophages of the central nervous system (CNS), including parenchymal microglia as well as CNS-associated macrophages (CAMs) such as meningeal (mMF) and perivascular macrophages (pvMF) are part of the CNS endogenous innate immune system that acts as the first line of defense during infections or trauma. It has been suggested that microglia and all CAM subsets are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAMs subsets in situ are poorly understood. Using novel fate mapping systems, single-cell profiling and cell-specific mutants, we show that only mMF and microglia share a common prenatal progenitor. In contrast, pvMF originate from perinatal mMF only after birth in an integrin-dependent manner. Furthermore, the establishment of pvMF critically requires the presence of vascular smooth muscle cells. In summary, our data reveal a novel precisely timed process in distinct anatomical niches for the establishment of CNS macrophage subsets.

2022-01-27 | GSE194433 | GEO

RNA sequencing data of microglia, meningeal macrophages (mMΦ) and perivascular macrophages (pvMΦ) isolated from brains of Cx3cr1-GFP mice at different age.

Project description:All tissue resident macrophages of the central nervous system (CNS), including parenchymal microglia as well as CNS-associated macrophages (CAMs) such as meningeal (mMF) and perivascular macrophages (pvMF) are part of the CNS endogenous innate immune system that acts as the first line of defense during infections or trauma. It has been suggested that microglia and all CAM subsets are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAMs subsets in situ are poorly understood. Using novel fate mapping systems, single-cell profiling and cell-specific mutants, we show that only mMF and microglia share a common prenatal progenitor. In contrast, pvMF originate from perinatal mMF only after birth in an integrin-dependent manner. Furthermore, the establishment of pvMFcritically requires the presence of vascular smooth muscle cells. In summary, our data reveal a novel precisely timed process in distinct anatomical niches for the establishment of CNS macrophage subsets.

2022-01-27 | GSE194432 | GEO

Specification of CNS macrophage subsets occurs postnatally in defined anatomical niches

Project description:All tissue resident macrophages of the central nervous system (CNS), including parenchymal microglia as well as CNS-associated macrophages (CAMs) such as meningeal (mMF) and perivascular macrophages (pvMF) are part of the CNS endogenous innate immune system that acts as the first line of defense during infections or trauma. It has been suggested that microglia and all CAM subsets are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAMs subsets in situ are poorly understood. Using novel fate mapping systems, single-cell profiling and cell-specific mutants, we show that only mMF and microglia share a common prenatal progenitor. In contrast, pvMF originate from perinatal mMF only after birth in an integrin-dependent manner. Furthermore, the establishment of pvMF critically requires the presence of vascular smooth muscle cells. In summary, our data reveal a novel precisely timed process in distinct anatomical niches for the establishment of CNS macrophage subsets.

2022-01-26 | GSE195437 | GEO

Microproteomics application for the limited number of cells

Project description:Mass spectrometry (MS)-based proteomics explores in-depth proteome, however, the analysis of cell subsets, which might be minor population, is hampered due to a multistep procedure for sample preparation and purification. Along those lines, optimization of proteomics workflow toward limited number of cells is an asset. Here, we report our workflow of microproteomics, proteomics for a limited number of cells: a microfluidic-chip based cell sorter was applied for a damage-free cell sorting, and each 100 or 1000 THP-1 cells were collected in hydrophilic or albumin-coated microtubes. Following in-solution enzymatic digestions, peptide mixtures were purified and applied to nanoLC-MS (Orbitrap Elite) analysis with 3 hr gradient. Our method enabled proteome mapping from 1000-sorted cells, with a similar in-depth map from 1 μg of cell lysate. This approach would be useful for cell subsets and limited materials such as circulating tumor cells, inflammatory cells in cancer tissues and clinical materials.

2017-07-18 | PXD005096 | JPOST Repository

Gene expression data from MDSC subsets, cell lines and tumor cells

Project description:We demonstrate that monocytic and granulocytic subsets of myeloid derived suppressor cells (mMDS, gMDSC) infiltrated in the primary tumor and distant organs with different time kinetics regulate spatiotemporal tumor plasticity. Using co-culture experiments and syngeneic mouse models, we provide evidence that tumor infiltrated mMDSCs facilitate tumor cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and in turn promote tumor cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumor bearing animals significantly enhance metastatic growth of already disseminated tumor cells. A “metastatic gene signature” identified in aggressive murine tumors following co-culture with MDSC subsets predicts poor patient survival in majority of human solid tumors suggesting clinical implications of our studies.

2016-05-21 | GSE81701 | GEO

Protocol for cell surface biotinylation of magnetic labeled and captured human peripheral blood mononuclear cells

Project description:Analysis of the surfaceome of a blood cell subset requires cell sorting, followed by surface protein enrichment. Here, we present a protocol combining magnetically activated cell sorting (MACS) and surface biotinylation of the target cell subset from human peripheral blood mononuclear cells (PBMCs). We describe the steps for isolating target cells and their in-column surface biotinylation, followed by isolation and mass spectrometry analysis of biotinylated proteins. The protocol enables in-column surface biotinylation of specific cell subsets with minimal membrane disruption.

2022-11-08 | PXD038027 | Pride

RNA sequencing of tumor associated macrophages and T cells in clear cell renal cell carcinoma

Project description:Tumor associated macrophages and T cells were characterized in a cohort of 73 ccRCC and 5 healthy donors using mass cytometry. Macrophage and T cell subsets of interest were identified and sorted directly from samples known to contain a high frequency of these subsets. CD8+ PD-1- T cells (n=6), exhausted CD8+ PD-1+ T cells (n=6), control macrophages CD14+ HLA-DR+ CD204- CD38- CD206- (n=11) and a population of TAM characterized as CD14+ HLA-DR+ CD204+ CD38+ CD206- (n=6) were isolated using FACS sorting.

2017-05-04 | E-MTAB-5640 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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