Expression data from endothelial cells sorted from breast cancer cells MDA-MB231 as compared with normal endothelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE48786 | GEO | 2013/12/31
SECONDARY ACCESSION(S): PRJNA211641
REPOSITORIES: GEO
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Project description:We studied the crosstalk between tumor and endothelial cells to explore the role of tumor microenvironment on cancer growth and progression. As part of our investigation, we showed that contact-dependent interaction of endothelial cells with breast tumor cells triggered the differential expression of a large number of genes in endothelium. Endothelial and MDA-MB231 cells were co-cultured together under serum- cytokine-free environment for 5 days followed by sorting endothelial cells and extracting RNA for microarray analysis. All conditions were made in triplicate. Endothelial cells were obtained using the methods described in Seandel M. & Butler J.M., 2008. WCMC-Q Genomics Core
2013-12-31 | E-GEOD-48786 | biostudies-arrayexpress
Project description:We studied the crosstalk between tumor and endothelial cells to explore the role of tumor microenvironment on cancer growth and progression. As part of our investigation, we showed that contact-dependent interaction of endothelial cells with breast tumor cells triggered the differential expression of a large number of genes in endothelium. Endothelial and MDA-MB231 cells were co-cultured together under serum- cytokine-free environment for 5 days followed by sorting endothelial cells and extracting RNA for microarray analysis. All conditions were made in triplicate. Endothelial cells were obtained using the methods described in Seandel M. & Butler J.M., 2008. WCMC-Q Genomics Core
| S-ECPF-GEOD-48786 | biostudies-other
Project description:Endothelial cells and macrophages are known to engage in tight and specific interactions that contribute to the modulation of vascular function. Here we show that adult endothelial cells provide critical signals for the selective growth and differentiation of macrophages from several types of hematopoietic progenitor cells. The process features the formation of well-organized colonies that exhibit progressive differentiation from the center to the periphery and towards an M2-like phenotype, characterized by enhanced expression of Tie2 and CD206/Mrc1. These colonies are long-lived as long as the contact with the endothelium is maintained; removal of the endothelial monolayer results in rapid dissolution of the macrophage colonies. Not only the maintenance but also the formation of the colonies is strictly dependent on endothelial contact. We further found that M-CSF produced by the endothelium is critical for the expansion of the macrophage colonies and that blockade of M-CSF receptor impairs colony growth. Functional analyses indicate that these macrophages are capable of accelerating angiogenesis, promoting tumor growth and effectively engaging in tight associations with endothelial cells in vivo. These findings uncover a critical role of endothelial cells in the induction of macrophage differentiation and their ability to promote further polarization towards a proangiogenic phenotype. 8 samples were sequenced: bone marrow derived macrophages (BMDM) were stimulated with LPS, IL4, or none. Colony cells induced by endothelial cells for 7 days. Each was duplicated.
2012-12-31 | E-GEOD-39660 | biostudies-arrayexpress
Project description:We recently established a KAIMRC1 cell line that has unique features compared to the known breast cancer cell lines, MCF7 and MDA-MB231. To characterize it further, we investigated the expression profile of nuclear receptors and their respective co-factors in these cell lines. We confirm that in contrast to the triple negative cell line MDA-MB231, the MCF7 and KAIMRC1 are estrogen receptor alpha (ERa) and progesterone receptor alpha (PRa) positive, with significant lower expression of these receptors in KAIMRC1. KAIMRC1 cell is a vitamin D receptor (VDR) negative and V-ErbA-Related Protein 2 (EAR2) positive in contrast to MCF7 and MDA-MB231. Remarkably, the histone deacetylases (HDACs) are highly expressed in KAIRMC1 with HDAC6 and HDAC 7 are exclusively expressed in KAIMRC1 while thyroid hormone receptor-associated protein 80 (TRAP80), telomeric DNA binding protein 1 (TBP1) and TGF-beta receptor interacting protein (TRIP1) are absent in KAIMRC1 but present in MCF7 and MDA-MB231. In a luciferase reporter assay, the ERa coexpression is needed for estrogen receptor element (ERE)-luciferase activation by estradiol in KAIMRC1 but not in MCF7. The co-expression of exogenous Liver X receptor alpha (LXRa)/retinoid X receptor alpha (RXRa) are necessary for LXR responsive element (LXRE) activation by the GW3696 in the three cell lines. However, the activity of peroxisome proliferator-activated receptor response element (PPARE)-tk-luciferase reporter increased when peroxisome proliferator-activated receptors alpha (PPARa)/RXRa were coexpressed but the addition of PPARa agonist (GW7647) did not stimulate further the reporter. The signal of the PPARE reporter increased in a dose-dependent manner with rosiglitazone (PPARg agonist) in KAIMRC1, MCF7, and MDA-MB231 when the proliferator-activated receptors gamma (PPARg)/RXRa receptors were cotransfected. Retinoic acid-induced activation of retinoic acid receptor response element (RARE)-tk-luciferase is dependent on exogenous expression of retinoic acid receptor alpha (RARa)/RXRa heterodimer in MDA-MB 231 but not in MCF7 and KAIMRC1 cell lines. In the three cell lines, Bexarotene-induced retinoid X receptor response element (RXRE)-luciferase reporter activation was induced only if the RXRa/LXRa heterodimer were co-expressed. The vitamin D receptor response element (VDRE)-luciferase reporter activity showed another distinct feature of KAIMRC1, where only co-expression of exogenous vitamin D receptor (VDR)/RXRa heterodimer was sufficient to reach the maximum rate of activation of VDRE reporter. In the proliferation assay, nuclear receptors ligands showed a distinct effect on KAIMRC1 compared to MCF7 and MDA-MB231. Growth inhibition effects of used ligands suggest that KAIMRC1 correlate more closely to MDA-MB231 than MCF7. Vitamin D3, rosiglitazone, novel RXR compound (RXRc) and PPARa compound (GW6471) have the most profound effects. In conclusion, we showed that nuclear receptors are differentially expressed, activated and also their ligand produced distinct effects in KAIMRC1 compared to MCF7 and MDA-MB231. This finding gives us confidence that KAIMRC1 has a unique biological phenotype.
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Project description:Endothelial cells and macrophages are known to engage in tight and specific interactions that contribute to the modulation of vascular function. Here we show that adult endothelial cells provide critical signals for the selective growth and differentiation of macrophages from several types of hematopoietic progenitor cells. The process features the formation of well-organized colonies that exhibit progressive differentiation from the center to the periphery and towards an M2-like phenotype, characterized by enhanced expression of Tie2 and CD206/Mrc1. These colonies are long-lived as long as the contact with the endothelium is maintained; removal of the endothelial monolayer results in rapid dissolution of the macrophage colonies. Not only the maintenance but also the formation of the colonies is strictly dependent on endothelial contact. We further found that M-CSF produced by the endothelium is critical for the expansion of the macrophage colonies and that blockade of M-CSF receptor impairs colony growth. Functional analyses indicate that these macrophages are capable of accelerating angiogenesis, promoting tumor growth and effectively engaging in tight associations with endothelial cells in vivo. These findings uncover a critical role of endothelial cells in the induction of macrophage differentiation and their ability to promote further polarization towards a proangiogenic phenotype.
2012-12-31 | GSE39660 | GEO
Project description:Chen2006 - Nitric Oxide Release from
Endothelial Cells
This model is described in the article:
Theoretical analysis of
biochemical pathways of nitric oxide release from vascular
endothelial cells.
Chen K, Popel AS.
Free Radic. Biol. Med. 2006 Aug; 41(4):
668-680
Abstract:
Vascular endothelium expressing endothelial nitric oxide
synthase (eNOS) produces nitric oxide (NO), which has a number
of important physiological functions in the microvasculature.
The rate of NO production by the endothelium is a critical
determinant of NO distribution in the vascular wall. We have
analyzed the biochemical pathways of NO synthesis and
formulated a model to estimate NO production by the
microvascular endothelium under physiological conditions. The
model quantifies the NO produced by eNOS based on the kinetics
of NO synthesis and the availability of eNOS and its
intracellular substrates. The predicted NO production from
microvessels was in the range of 0.005-0.1 microM/s. This range
of predicted values is in agreement with some experimental
values but is much lower than other rates previously measured
or estimated from experimental data with the help of
mathematical modeling. Paradoxical discrepancies between the
model predictions and previously reported results based on
experimental measurements of NO concentration in the vicinity
of the arteriolar wall suggest that NO can also be released
through eNOS-independent mechanisms, such as catalysis by
neuronal NOS (nNOS). We also used our model to test the
sensitivity of NO production to substrate availability, eNOS
concentration, and potential rate-limiting factors. The results
indicated that the predicted low level of NO production can be
attributed primarily to a low expression of eNOS in the
microvascular endothelial cells.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000676.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000676 | BioModels
Project description:Chen2006 - Nitric Oxide Release from
Endothelial Cells
This model is described in the article:
Theoretical analysis of
biochemical pathways of nitric oxide release from vascular
endothelial cells.
Chen K, Popel AS.
Free Radic. Biol. Med. 2006 Aug; 41(4):
668-680
Abstract:
Vascular endothelium expressing endothelial nitric oxide
synthase (eNOS) produces nitric oxide (NO), which has a number
of important physiological functions in the microvasculature.
The rate of NO production by the endothelium is a critical
determinant of NO distribution in the vascular wall. We have
analyzed the biochemical pathways of NO synthesis and
formulated a model to estimate NO production by the
microvascular endothelium under physiological conditions. The
model quantifies the NO produced by eNOS based on the kinetics
of NO synthesis and the availability of eNOS and its
intracellular substrates. The predicted NO production from
microvessels was in the range of 0.005-0.1 microM/s. This range
of predicted values is in agreement with some experimental
values but is much lower than other rates previously measured
or estimated from experimental data with the help of
mathematical modeling. Paradoxical discrepancies between the
model predictions and previously reported results based on
experimental measurements of NO concentration in the vicinity
of the arteriolar wall suggest that NO can also be released
through eNOS-independent mechanisms, such as catalysis by
neuronal NOS (nNOS). We also used our model to test the
sensitivity of NO production to substrate availability, eNOS
concentration, and potential rate-limiting factors. The results
indicated that the predicted low level of NO production can be
attributed primarily to a low expression of eNOS in the
microvascular endothelial cells.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000676.
To cite BioModels Database, please use:
Chelliah V et al. BioModels: ten-year
anniversary. Nucl. Acids Res. 2015, 43(Database
issue):D542-8.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000676 | BioModels
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2024-06-01 | PXD052259 | Pride
Project description:Targeted therapies against mutant BRAF are effectively used in combination with MEK inhibitors (MEKi) to treat advanced melanoma. However, treatment success is affected by resistance and adverse events (AEs). Approved BRAF inhibitors (BRAFi) show high levels of target promiscuity, which can contribute to these effects. Blood vessels are in direct contact with high plasma concentrations of BRAFi, but effects of the inhibitors in this cell type are unknown. Hence, we aimed to characterize responses to clinically relevant BRAF kinase inhibitors in the vascular endothelium. A mass spectrometry-based analysis of the phosphoproteome of dermal microvascular endothelial cells revealed distinct sets of off-targets of the used BRAFi. Meanwhile, there were only negligible changes to the proteome after 1 h of treatment. Together with our published functional data, these findings provide insights on the surprisingly distinct side effects of BRAFi on endothelial signaling and functionality.
2024-06-01 | PXD052251 | Pride
Project description:Endothelial inflammation contributes to the pathogenesis of numerous human diseases; however, the role of tumor endothelial inflammation in the growth of experimental tumors and its influence on the prognosis of human cancers is less understood. TNF-M-NM-1, an important mediator of tumor stromal inflammation, is known to target the tumor vasculature. In this study, we demonstrate that B16-F1 melanomas grew more rapidly in C57BL/6 wild-type (WT) mice than in syngeneic mice with germline deletions of both TNF-M-NM-1 receptors (KO). This enhanced tumor growth was associated with increased COX2 inflammatory expression in WT tumor endothelium compared to endothelium in KO mice. We purified endothelial cells from WT and KO tumors and characterized dysregulated gene expression, which ultimately formed the basis of a 6-gene Inflammation-Related Endothelial-derived Gene (IREG) signature. This inflammatory signature expressed in WT tumor endothelial cells was trained in human cancer datasets and predicted a poor clinical outcome in breast cancer, colon cancer, lung cancer and glioma. Consistent with this observation, conditioned media from human endothelial cells treated with pro-inflammatory cytokines (TNF-M-NM-1 and interferons) accelerated the growth of human colon and breast tumors in immune-deprived mice as compared with conditioned media from untreated endothelial cells. These findings demonstrate that activation of endothelial inflammatory pathways contributes to tumor growth and progression in diverse human cancers. To investigate the genes associated with TNF-M-NM-1 signaling in tumor endothelium, we performed expression profiling of tumor-associated endothelial cells isolated from B16F1 tumors grown in syngeneic TNFR 1, 2 -/- (KO) and C57BL/6 (WT) mice. Tumor endothelial cells were isolated from WT and KO tumors when tumor volumes were ~180 mm^3. This was based on a stepwise immunopurification of combined tumor tissue (Seaman, S. et al. Genes that distinguish physiological and pathological angiogenesis. Cancer Cell 11, 539-54 (2007)). Tumor endothelial cells were lysed to collect total RNA and analyzed in duplicates with Affymetrix GeneChipM-BM-. Mouse Genome 430 2.0 Arrays.
2012-10-20 | E-GEOD-33253 | biostudies-arrayexpress