Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment

ABSTRACT: Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transitionrelated genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148483 | GEO | 2020/04/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment

Project description:Tumor cells interact with the microenvironment that specifically supports and promotes tumor development. Key components in the tumor environment have been linked to various aggressive cancer features and can further influence the presence of subpopulations of cancer cells with specific functions, including cancer stem cells and migratory cells. To model and further understand the influence of specific microenvironments we have developed an experimental platform using cell-free patient-derived scaffolds (PDSs) from primary breast cancers infiltrated with standardized breast cancer cell lines. This PDS culture system induced a series of orchestrated changes in differentiation, epithelial-mesenchymal transition, stemness and proliferation of the cancer cell population, where an increased cancer stem cell pool was confirmed using functional assays. Furthermore, global gene expression profiling showed that PDS cultures were similar to xenograft cultures. Mass spectrometry analyses of cell-free PDSs identified subgroups based on their protein composition that were linked to clinical properties, including tumor grade. Finally, we observed that an induction of epithelial-mesenchymal transition-related genes in cancer cells growing on the PDSs were significantly associated with clinical disease recurrences in breast cancer patients. Patient-derived scaffolds thus mimics in vivo-like growth conditions and uncovers unique information about the malignancy-inducing properties of tumor microenvironment.

2020-06-25 | PXD018367 | Pride

Proteomics of cell-free patient-derived scaffolds from breast cancer identify clinically relevant imprinted proteins and cancer-progressing properties

Project description:Breast cancer is a heterogenous disease that is difficult to model in vitro. Frozen primary breast cancers were decellularised to generate patient-derived scaffolds which are used to model 3D growth for cancer cell lines. The cell-free cancer microenvironments in the patient-derived scaffolds influence breast cancer cell line phenotypes and enrich for cells with cancer stem cell characteristics. Growth in patient-derived scaffold cultures also influenced the expression of epithelial-to-mesenchymal transition-related genes, and several gene expression changes in the model could be associated to clinical parameters of the original tumors and corresponding patients. Previous studies also demonstrated that the relative protein composition in the cell-free cancers were related to tumor grade and proliferation in cancer cells, suggesting that the relative proteomic composition varies between individual microenvironments. Therefore, we decellularised a larger breast cancer cohort to better characterize the cell-free microenvironments and potentially link to clinical features of the tumors and patients, which could be used to identify novel processes and targets that could be used to better model the disease or targeted in drug discovery.

2024-04-18 | PXD042671 | Pride

A tissue-engineered mimic of the ovarian cancer microenvironment of increases cell proliferation and tumor growth.

Project description:Using tissue engineering technologies, we aimed to engineer the ovarian tumor microenvironment to study disease progression by combining biomimetic hydrogels with melt electrospun written scaffolds. 3D co-cultures were constructed by assembling ovarian cancer cell-laden hydrogels with mesothelial cell-layered scaffolds. 3D constructs were characterised by proliferation and transcriptomic analyses and applied to an intraperitoneal xenograft model. Increased cancer cell proliferation upon 3D co-cultures was validated using patient-derived cells and linked to greater tumor burden in vivo. Genome-wide microarray analysis identified IGFBP7, PTGS2, VEGFC and FGF2 as being upregulated in 3D co-cultures compared to 3D mono-cultures. Protein expression of these differentially regulated factors was confirmed by immunohistochemistry in xenograft and patient-derived tumor tissues and correlated with overall and progression-free survival. This pre-clinical cancer model harbors the complexity of the disease seen in patients and advances our understanding of the underlying cell biology and the contribution of the tumor microenvironment to cancer growth.

2018-01-25 | GSE109577 | GEO

Porcine breast extracellular matrix hydrogel for spatial tissue culture

Project description:Porcine mammary fatty tissues represent an abundant source of biomaterial for generation of breast-specific extracellular matrix (ECM). Here we report the extraction of total ECM proteins from pig breast fatty tissues, the fabrication of hydrogel scaffolds from the extracted ECM proteins, the structural properties of the scaffolds, and the applications of the hydrogel in human mammary epithelial cell spatial cultures for cell surface receptor expression, metabolomics characterization, acini formation, proliferation, migration between different scaffolding compartments, and in vivo tumor formation. This model system provides an additional option for studying human breast diseases such as breast cancer.

2019-11-12 | PXD010960 | Pride

Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics (part III)

Project description:Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using 13C6-glucose, 13C-1+2-glucose, 13C5,15N2-Gln, 13C3-glycerol, and 13C8-octanoate as tracers. These tracers were designed to probe the central energy producing and anabolic pathways (glycolysis, pentose phosphate pathway, Krebs Cycle, glutaminolysis, nucleotide synthesis and lipid turnover). We found that glycolysis was not associated with the rate of breast cancer cell proliferation, glutaminolysis did not support lipid synthesis in primary breast or breast cancer cells, but was a major contributor to pyrimidine ring synthesis in all cell types; anaplerotic pyruvate carboxylation was activated in breast cancer versus primary cells. We also found that glucose metabolism in individual breast cancer cell lines differed between in vitro cultures and tumor xenografts, but not the metabolic distinctions between cell lines, which may reflect the influence of tumor architecture/microenvironment.

2018-01-24 | ST000928 | MetabolomicsWorkbench

Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics (part II)

2018-01-24 | ST000927 | MetabolomicsWorkbench

Probing the metabolic phenotype of breast cancer cells by multiple tracer stable isotope resolved metabolomics (part I)

2018-01-22 | ST000926 | MetabolomicsWorkbench

Characterisation of a cell-free myxoid liposarcoma patient-derived xenograft scaffold model

Project description:Myxoid liposarcoma (MLS) is the second most common type of liposarcoma, and today few model systems to study the disease exists. To be able to model the disease in vitro, cell-free scaffolds from MLS patient-derived xenograft (PDX) models were generated. The MLS scaffolds were then used as a 3D growth platform for MLS cell lines to study the cancer microenvironments impact on cellular heterogeneity using RNA sequencing. Key components in the microenvironment have also been shown to influence the fraction of cellular subpopulations, such as cancer stem cells and migratory cells but also to promote aggressive features of cancers. Therefore, to better understand and characterize these scaffolds, protein analyses were performed and links between scaffold compositions and the induced gene expression profiles of the cells grown therein could be made. This model system provides a better insight to the composition of the cell-free cancer microenvironment in a rare disease, which can lead to identification of novel malignancy inducing properties in MLS.

2024-05-08 | PXD023792 | Pride

Development of an immune-related prognostic biomarker for triple-negative breast cancer

Project description:Triple-negative breast cancer represents approximately 15–20% of all reported breast cancer cases, and is characterized by a shorter survival time and higher mortality rates compared to other breast cancer sub-types. Tumor microenvironment (TME) refers to the internal and external environment of tumor tissue. Increasing evidence indicates that a tumor’s microenvironment is tightly associated with the immunological surveillance and defense during the development of breast cancer. Although oncology studies employing digital dissection methodologies have provided some insight on the biological features of TME, the development of methods to investigate the cellular composition of the tumor microenvironment remain an important research priority. In this study, we extracted whole transcriptome from 30 Triple-negative breast cancer (TNBC) patients and then used bioinformatics approaches to characterize cell type content in tumor tissue compared with para-cancerous tissue. We identified 4 types of enriched immune cells and 6 types of downregulated immune cells in the tumor tissue samples. After comprehensive bioinformatics analyses, we developed an ‘immune infiltration score’ (IIS) to quantitatively model immune cell infiltration in TNBC. To demonstrate the utility of the IIS, we used 2 independent datasets for validation. We found that patients with a higher IIS showing a longer progression-free survival time and significantly better prognosis than those with a lower IIS value. In sum, we explored the immune infiltration landscape in 30 TNBC patients and provided a novel and reliable biomarker IIS to evaluate the progression-free survival and prognosis in the TNBC patients.

2021-10-18 | E-MTAB-10886 | biostudies-arrayexpress

Microenvironmental Stiffness Induces Metabolic Reprogramming in Glioblastoma

Project description:The mechanical properties of solid tumors influence tumor cell phenotype and ability to invade into surrounding tissues. Using bioengineered scaffolds to provide a matrix microenvironment for patient-derived glioblastoma (GBM) spheroids, this study demonstrates that a soft, brain-like matrix induces GBM cells to shift to a glycolysis-weighted metabolic state which supports invasive behavior. We first show that orthotopic murine GBM tumors are stiffer than peri-tumoral brain tissues, but tumor stiffness is heterogenous where tumor edges are softer than the tumor core. Then, we developed three-dimensional scaffolds with µ-compressive moduli resembling either stiffer, tumor core or softer, peri-tumoral brain tissue. We demonstrate that the softer matrix microenvironment induces a shift in GBM cell metabolism toward glycolysis which manifests in lower proliferation rate and increased migration activities. Finally, we show that these mechanical cues are transduced from the matrix via CD44 and integrin receptors to induce metabolic and phenotypic changes in cancer cells.

2023-08-02 | GSE239610 | 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