Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lipidomic Comparison of 2D and 3D Colon Cancer Cell Culture Models

ABSTRACT: Altered lipid metabolism is one of the hallmarks of cancer. Cellular proliferation and de novo synthesis of lipids are related to cancer progression. In this study, we evaluated the lipidomic profile of two-dimensional (2D) monolayer and multicellular tumor spheroids from the HCT 116 colon carcinoma cell line. We utilized serial trypsinization on the spheroid samples to generate three cellular populations representing the proliferative, quiescent, and necrotic regions of the spheroid. This analysis enabled a comprehensive identification and quantification of lipids produced in each of the spheroid layer and 2D cultures. We show that lipid subclasses associated with lipid droplets form in oxygen-restricted and acidic regions of spheroids and are produced at higher levels than in 2D cultures. Additionally, sphingolipid production, which is implicated in cell death and survival pathways, is higher in spheroids relative to 2D cells. Finally, we show that increased numbers of lipids comprised of polyunsaturated fatty acids (PUFAs) are produced in the quiescent and necrotic regions of the spheroid. The lipidomic signature for each region and cell culture type highlights the importance of understanding the spatial aspects of cancer biology. These results provide additional lipid biomarkers in the tumor microenvironment that can be further studied during potential therapeutic studies which target pivotal lipid production pathways.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Cultured Cells

DISEASE(S): Cancer

SUBMITTER: Fernando Tobias

PROVIDER: ST002070 | MetabolomicsWorkbench | Sun Jan 30 00:00:00 GMT 2022

REPOSITORIES: MetabolomicsWorkbench

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	mwtab	Other

Items per page:

1 - 1 of 1

Similar Datasets

Glycosphingolipid synthesis mediates immune evasion in Kras-driven cancer

Project description:Cancer cells frequently alter their lipids to grow and adapt to their environment1–3. Despite the critical functions of lipid metabolism in membrane physiology, signaling, and energy production, how specific lipids contribute to tumorigenesis is incompletely understood. Here, using functional genomics and lipidomic approaches, we identified de novo sphingolipid synthesis as an essential pathway for cancer immune evasion. Synthesis of sphingolipids is surprisingly dispensable for cancer cell proliferation in culture or in immunodeficient mice but required for tumor growth in multiple syngeneic models. Blocking sphingolipid production in cancer cells enhances the anti-proliferative effects of natural killer (NK) and CD8+ T cells partly via interferon gamma (IFNg) signaling. Mechanistically, depletion of glycosphingolipids increases surface levels of IFNg receptor subunit 1 (Ifngr1), mediating IFNg-induced growth arrest and proinflammatory signaling. Finally, pharmacological inhibition of glycosphingolipid synthesis synergizes with checkpoint blockade therapy to enhance anti-tumor immune response. Altogether, our work identifies glycosphingolipids as necessary and limiting metabolites for cancer immune evasion.

2024-06-30 | GSE270660 | GEO

Glycosphingolipid synthesis mediates immune evasion in Kras-driven cancer

2024-06-26 | PXD052718 | Pride

Expression Analysis of 2D, 3D Quiescent, and 3D Activated Pancreatic Stellate Cells

Project description:This study used Illumina single-end RNA-sequencing to examine gene expression differences between 2 mouse-derived pancreatic stellate cell lines (PSC4, PSC5) grown either in 2D monolayers, as 3D quiescent cultures, or as 3D activated transwell cocultures with 2 mouse tumor-derived pancreatic ductal organoid lines (T4, T5). Mouse pancreatic stellate cell (PSC) lines were derived from the pancreata of wild-type C57Bl/6J mice. Mouse tumor organoid lines were derived from mouse pancreata containing pancreatic ductal adenocarcinoma (PDAC) from the KrasLSL-G12D; Trp53LSL-R162H; Pdx1-Cre mouse model. We measured genes differentially expressed among 2D, quiescent, and 3D activated PSCs that may reflect the expression changes of heterogeneous CAF population in pancreatic tumors.

2017-02-03 | GSE93313 | GEO

Gene expression profile of mouse Lewis lung carcinoma cell line cultivated in 2-dimensional or 3-dimensional cell culture enriched with laminin rich extracellular matrix proteins.

Project description:Obvious advantages of 3D cell culture model are the cell morphology better reflecting tissue cell morphology, the formation of zones of i) active proliferation, ii) quiescent viable cell zone and iii) necrotic zone, as well as formation of nutrition, oxygen and drug gradients better reflecting cellular environment in tissue. Nevertheless the 3D cultures are a model still not resembling full complexity of tumor tissue environment in vivo. Few obvious limitations of 3D cell cultures as cancer research model are the lack of vasculature, host immune response and other cell-cell interactions that occur between cancer and stromal cells in tumors. Recognized advantages and limitations of the 3D cell culture models, however do not suggest directly the areas of cancer biology where 3D models could be applied with highest success. Hence detailed analysis at the molecular level of 2D/3D cell cultures and tumors in vivo are needed to unlock the power of 3D cell culture model. In order to elucidate which biological pathways of cancer cells in tumors are best resembled by the 3D cell culture model we have analyzed whole genome gene expression changes in mouse LLC1 cell line when cultured in 2D or laminin rich ECM 3D system. RNA was isolated 48h after growing in two different cell culture systems.

2015-12-10 | E-GEOD-75863 | biostudies-arrayexpress

Knocking down CAVIN1 in WPMY-1 normal prostate stromal cells

Project description:Lipid uptake occurs through caveolae, plasma membrane invaginations formed by caveolins (CAV) and caveolae-associated protein 1 (CAVIN1). Genetic alterations of CAV1N1 and CAV1 modify lipid metabolism and underpin lipodystrophy syndromes. Lipids contribute to tumorigenesis by providing fuel to cancer metabolism and supporting growth and signaling. Tumor stroma supports tumor proliferation, invasion and metastasis but how stromal lipids influence these processes remain to be defined. Here we show that stromal CAVIN1 regulates lipid abundance in the prostate cancer microenvironment and suppresses metastasis. We show that depletion of CAVIN1 in prostate stromal cells markedly reduces their lipid droplet accumulation and increases inflammation.

2022-01-19 | GSE146229 | GEO

Gene expression profile of mouse Lewis lung carcinoma cell line cultivated in 2-dimensional or 3-dimensional cell culture enriched with laminin rich extracellular matrix proteins.

2015-12-10 | GSE75863 | GEO

Bioreactor-engineered cancer tissues mimic phenotypes, gene expression profiles and drug resistance mechanisms detectable in xenografts and clinical specimens.

Project description:Cancer tissue-like structures were developed by using established human tumor cell lines in perfusion-based bioreactor systems. In colorectal cancer (CRC) cell lines, perfusion allowed more homogeneous scaffold seeding than tri-dimensional (3D) static cultures and significantly (13.7 fold, p<0.0001) higher proliferation. Resulting tissues exhibited morphology and phenotypes similar to xenografts generated in immunodeficient mice. Whole transcriptome analysis of 2D, 3D static and 3D perfusion cultures revealed the highest correlation between xenografts and 3D perfusion cultures (r=0.985). Clinically relevant concentrations of 5-FU, used in neo- and adjuvant CRC treatment, had no effect on numbers of HT-29 CRC cells cultured in 3D perfusion or xenografts, as compared with a 55.8% reduction in 2D cultures. Treatment induced apoptosis in 2D cultures, but only “nucleolar stress” in perfused cells and xenografts, consistent with partial responsiveness. In 3D perfusion cultures BCL-2, TRAF1, and FLIP gene expression was marginally affected, as compared with significant down-regulation in 2D cell cultures. Accordingly, ABT-199 BCL-2 inhibitor, induced cytostatic effects in 3D perfusion but not in 2D cell cultures (p=0.003). Tumor cells from partially responsive (Dworak 2) patients undergoing neo-adjuvant treatment, typically (10/11) expressed BCL-2, as compared with 0/3 highly (Dworak 3-4) responsive and 4/15 fully resistant CRC (Dworak 0/1, p=0.03), closely matching 3D perfusion cultures data. These results indicate that 3D perfusion cultures efficiently mimic phenotypic and functional features observed in xenografts and clinical specimens. These models may be of critical translational relevance to address fundamental human tumor cell biology issues and to develop predictive pre-clinical tests of novel compounds.

2016-01-25 | GSE57961 | GEO

Multi-OMIC analysis of brain and serum from chronically-stressed mice

Project description:Major depressive disorder (MDD) is a complex condition with unclear pathophysiology. Molecular disruptions within the periphery and limbic brain regions contribute to depression symptomatology. Here, we utilized a mouse chronic stress model of MDD and performed metabolomic, lipidomic, and proteomic profiling on serum plus several brain regions (ventral hippocampus, nucleus accumbens, and prefrontal cortex) of susceptible, resilient, and unstressed control mice. Proteomic analysis identified three serum proteins reduced in susceptible animals; lipidomic analysis detected differences in lipid species between resilient and susceptible animals in serum and brain; and metabolomic analysis revealed pathway dysfunctions of purine metabolism, beta oxidation, and antioxidants, which were differentially associated with stress susceptibility vs resilience by brain region. Antidepressant treatment ameliorated MDD-like behaviors and affected key metabolites within outlined networks, most dramatically in the ventral hippocampus. This work presents a resource for chronic stressinduced, tissue-specific changes in proteins, lipids, and metabolites and illuminates how molecular dysfunctions contribute to individual differences in stress sensitivity

2021-09-08 | PXD013146 | Pride

Acetyl-CoA Carboxylase Obstructs CD8+ T-Cell Lipid Utilization in the Tumor Microenvironment

Project description:The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor infiltrating T cells (TILs) hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control.However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors. Using patient samples and mouse models, we reveal that the solid TME imposes perpetual acetyl-CoA carboxylase (ACC) activity, invoking lipid biogenesis and storage in TILs that directly opposes FAO. Using metabolic, lipidomic, and confocal imaging strategies, we find that restricting ACC rewires T cell metabolism, enabling energy maintenance in TME stress. Moreover, limiting ACC activity potentiates a gene and phenotypic program indicative of T cell longevity, engendering T cells with increased survival and polyfunctionality, with the ability to control solid cancer.

2024-03-05 | GSE254000 | GEO

UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma [shRNA]

Project description:Using pooled shRNA libraries we performed a focused screen of 115 genes in 3D ex vivo cultures of primary murine lung tumor cells and 2D cultures of murine LKR10 cells. These screens identify Uhrf1 as gene selectively important for the 3D growth of primary lung cancer spheroids.

2023-05-15 | GSE209923 | 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