Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell sequencing reveals the landscape of the brain metastatic microenvironment

ABSTRACT: Our analysis identifies intratumoral components that are predominantly tumor cells, fibroblasts, myeloid cells, stromal cells that express neural stem cell (NSC) markers, with minor populations of oligodendrocytes (oligo) and T cells. Different samples present diverse cell compositions, indicating the underlying cellular interactions that affect different cellular infiltration within TME. Importantly, we identify the tumor-associated fibroblasts in both in-house and external scRNA-seq datasets that 1) highly expresses type I collagen genes; 2) dominates the cell-cell interactions in TME through the type I collagen signaling axis; and 3) remodels the TME to a collagen-I-rich extracellular matrix (ECM) similar to the original TME at the primary sites. We also observe the M1 activation of the native microglial cells and the infiltrated macrophages, which may create a proinflammatory TME and be responsible for the high expression of collagen type I in fibroblasts. Moreover, the tumor cell-specific receptors are significantly associated with patients’ survival in both brain metastasis and the native glioblastoma cases. Overall, our analyses identify the type I collagen secreting tumor-associated fibroblasts as a key mediator in metastatic brain tumors and reveal the involved tumor receptors associated with patients’ survival. Our discoveries provide potential biomarkers for effective therapeutic targets and intervention strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234832 | GEO | 2023/07/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Mesothelioma-associated fibroblasts enhance proliferation and migration of malignant pleural mesothelioma cells via Met/PI3K and WNT signaling but do not protect against cisplatin

Project description:Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis. Unlike many other cancers, MPM is mostly characterized by inactivation of tumor suppressor genes. Its highly malignant nature in absence of tumor driving oncogene mutations indicates an extrinsic supply of stimulating signals by cells of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are an abundant cell type of the TME and have been shown to drive the progression of several cancer types. The aim of the current study was to isolate and characterize patient-derived mesothelioma-associated fibroblasts (Meso-CAFs), and evaluate their impact on MPM cells.

2022-12-31 | E-MTAB-12179 | biostudies-arrayexpress

Human Prostate Cancer epithelial-fibroblast cell signalling by CTAP-MS

Project description:A greater understanding of cell signaling events that occur within the prostate cancer tumor microenvironment (TME), for example between cancer-associated fibroblasts (CAFs) and prostate epithelial or cancer cells, may identify novel biomarkers and more effective therapeutic strategies for this disease. To address this, we used cell-type specific labelling with amino acid precursors (CTAP) to define cell type-specific phosphoproteomic changes that occur when prostate epithelial cells are co-cultured with normal patient-derived prostate fibroblasts (NPFs) versus matched CAFs.

2023-03-11 | PXD037272 | Pride

Spatially distinct reprogramming of the tumor microenvironment based on tumor invasion in diffuse-type gastric cancers

Project description:The invasive potential of gastric cancers (GCs) defines the hallmarks of malignancies; however, the cellular components and their molecular features associated with tumor invasiveness in GC microenvironments (TME) are poorly understood. In this study, we constructed a comprehensive atlas of 23,060 single cells obtained from surgically dissected superficial and deep layers of five diffuse-type GC along with matched normal. As a result, seven major cell types were identified. Fibroblasts, endothelial cells, and myeloid cells were categorized as being enriched in the deep layers. Cell type-specific clustering further revealed that the superficial-to-deep layer transition is associated with enrichment in inflammatory endothelial cells and fibroblasts with upregulated CCL2 transcripts. This study reveals the spatial reprogramming of the TME that may underlie invasive tumor potential in diffuse-type GC. This TME profiling across tumor layers suggests new targets, such as CCL2, that can modify the TME to inhibit tumor progression in diffuse-type GC.

2021-08-09 | GSE167297 | GEO

IL-33 provision by reprogrammed tumor fibroblastic stromal cells promotes local T cell activity and facilitates melanoma eradication

Project description:The tumor microenvironment (TME) is a complex mixture of tumor cells, immune cells, endothelial cells and fibroblastic stroma cells (FSC). While cancer-associated fibroblasts are generally seen as a tumor-promoting entity, it is conceivable that distinct FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intra-tumoral injection of a recombinant LCMV-based vaccine vector (r3LCMV) expressing the melanocyte differentiation antigen TRP2 results in T cell-dependent eradication of melanomas. Analysis of the TME revealed that viral vector transduction precipitates activation of particular FSC subsets. Using single-cell RNA-seq analysis, we identified a Cxcl13-expressing FSC population with a pronounced immune-stimulatory signature and increased expression of the inflammatory cytokine IL-33. Genetic ablation of Il33 in Cxcl13-Cre+ FSC impeded functionality of intratumoral T cells and consequently tumor control. Thus, reprogramming of distinct FSC subsets in the TME through LCMV-based vectors efficiently promotes tumor eradication by locally sustaining the activity of tumor-specific T cells.

2021-07-03 | E-MTAB-9407 | biostudies-arrayexpress

Epidermolysis bullosa associated cutaneous SCC fibroblast expression profiling

Project description:Patients with the genetic skin blistering disease recessive dystrophic epidermolysis bullosa (RDEB) develop aggressive cutaneous squamous cell carcinoma (cSCC). Metastasis leading to mortality is greater in RDEB than in other patient groups with cSCC. Here we investigate the dermal component in RDEB using mRNA expression profiling to compare cultured fibroblasts isolated from individuals without cSCC and directly from tumor matrix in RDEB and non-RDEB samples. While gene expression of RDEB normal skin fibroblasts resembled that of cancer-associated fibroblasts, RDEB cancer-associated fibroblasts exhibited a distinct and divergent gene expression profile, with a large proportion of the differentially expressed genes involved in matrix and cell adhesion. RDEB cancer-associated fibroblasts conferred increased adhesion and invasion to tumor and non-tumor keratinocytes. Reduction of COL7A1, the defective gene in RDEB, in normal dermal fibroblasts led to increased type XII collagen, thrombospondin-1 and Wnt-5A, while re-expression of wild type COL7A1 in RDEB fibroblasts decreased type XII collagen, thrombospondin- 1, and Wnt-5A expression, reduced tumor cell invasion in organotypic culture, and restricted tumor growth in vivo. Overall our findings demonstrate that matrix composition in patients with RDEB is a permissive environment for tumor development, and type VII collagen directly regulates the composition of matrix proteins secreted by dermal and cancer-associated fibroblasts. 16 samples

2012-05-15 | E-GEOD-37738 | biostudies-arrayexpress

Epidermolysis bullosa associated cutaneous SCC fibroblast expression profiling

2012-05-16 | GSE37738 | GEO

Bone marrow-derived multipotent mesenchymal stromal cells promote tongue cancer invasion by inducing collagen production

Project description:Tumor microenvironment (TME) is an active player in malignant growth and spread. Changes in the composition and structure of TME and extracellular matrix can result in either suppression or facilitation of malignant tumor growth. Carcinoma‐associated fibroblasts, bone marrow-derived multipotent mesenchymal stromal cells (BMMSCs), tumor associated macrophages and other inflammatory cells all affect the composition of TME, proliferation and survival of cancer cells, angiogenesis, invasion and metastasis. The objective of this work was to investigate the effect of the interaction between bone marrow-derived BMMSCs and human oral tongue squamous cell carcinoma (OTSCC) cells in the processes of invasion and gene expression. Co-cultures of OTSCC cancer cells and BMMSCs in 3D organotypic invasion assay were used in addition to cell culture, immunological, microarray, and RNA interference techniques. Total number of 4 samples were analyzed. 2 replicates of cultured human oral tongue squamous cell carcinoma (OTSCC) cells, and 2 replicates of OTSCC cells co-cultured with bone marrow-derived multipotent mesenchymal stromal cells

2013-12-01 | E-GEOD-44458 | biostudies-arrayexpress

Stromal evolution of cancer-associated fibroblasts in PDAC GEMMs

Project description:With the advent of cancer immunotherapy, intense investigation has been focused on tumor-infiltrating immune cells. With only a fraction of patients responding to these new therapies, a better understanding of all elements of the tumor microenvironment (TME) that may influence therapeutic outcome is needed. Stromal elements of the TME, chiefly fibroblasts, have emerged as potential contributors to tumor progression and most recently resistance to immunotherapy, but their precise composition and clinical relevance remain incompletely understood. Here we use single-cell transcriptomics to chart the fibroblastic landscape during pancreatic ductal adenocarcinoma (PDAC) progression in animal models, identifying two healthy tissue fibroblast subsets that co-evolve along individual trajectories into four subsets of carcinoma-associated fibroblasts (CAFs).

2019-10-31 | E-MTAB-8483 | biostudies-arrayexpress

Targeting stromal cell sialylation reverses T cell mediated immunosuppression in the tumor microenvironment

Project description:Immunosuppressive tumor microenvironments (TME) reduce the effectiveness of immune responses in cancer. Mesenchymal stromal cells (MSC), precursors to cancer-associated fibroblasts (CAFs), dictate tumor progression by enhancing immune cell suppression in colorectal cancer (CRC). Hyper-sialylation of glycans promotes immune evasion in cancer through binding of sialic acids to their receptors, Siglecs, expressed on immune cells that results in inhibition of effector functions. The role of sialylation in dictating MSC/CAF immunosuppression in the TME is unknown. In this study, we show that tumor-conditioned stromal cells have increased sialyltransferase expression, α2,3/6-linked sialic acid and Siglec ligands. Tumor-conditioned stromal cells and CAFs induce exhausted immunomodulatory PD-1, Siglec-7 and Siglec-9-expressing T cell phenotypes. In vivo, targeting stromal cell sialylation reverses stromal cell-mediated immunosuppression, as evidenced by infiltration of CD25 and granzyme B-expressing T cells in the tumor and draining lymph node. Targeting stromal cell sialylation may overcome immunosuppression in the CRC TME.

2023-05-22 | GSE229054 | GEO

Microenvironment Shapes Small Cell Lung Cancer Neuroendocrine States and Presents Unique Therapeutic Opportunities

Project description:Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intra-tumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the tumor microenvironment (TME) exhibits substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAF) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting an exceptionally poor prognosis. Together, our work provides the first comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLCs adaptable nature, opening possibilities for re-programming the intercellular communications that shape SCLC tumor states.

2024-05-15 | PXD052033 | Pride

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