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Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

ABSTRACT: we examined how HS-reduced vascular endothelial cells are involved in the proliferation of glioma by using mice in which Ext-1 expression is specifically suppressed in vascular endothelial cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE175419 | GEO | 2021/11/17

REPOSITORIES: GEO

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Fibroblast-specific reduction of heparan sulfate suppresses pancreatic cancer growth in mice

Project description:we examined how HS-reduced fibroblasts are involved in the proliferation of pancreatic cancer by using mice in which Ext-1 expression is specifically suppressed in fibroblasts.

2022-06-13 | GSE203598 | GEO

Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth in mice

Project description:we examined how HS-reduced fibroblasts are involved in the proliferation of colon cancer by using mice in which Ext-1 expression is specifically suppressed in fibroblasts.

2022-06-13 | GSE203597 | GEO

Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

Project description:Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

| PRJNA732371 | ENA

Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice.

Project description: Not available

| S-EPMC8585801 | biostudies-literature

TFCP2 is a transcriptional regulator of heparan sulfate assembly and melanoma cell growth

Project description:Heparan sulfate (HS) is a long, linear polysaccharide that is ubiquitously expressed in all animal cells and plays a key role in many cellular processes, including cell signaling and development. Dysregulation of HS assembly has been implicated in pathophysiological conditions, such as tumorigenesis and rare genetic disorders. HS biosynthesis occurs in a non-template driven manner in the endoplasmic reticulum and Golgi through the activity a large group of biosynthetic enzymes. While much is known about its biosynthesis, little is understood about the regulation of HS assembly across diverse tissue types and disease states. To address this gap in knowledge, we recently performed genome-wide CRISPR/Cas9 screens to identify novel regulatory factors of HS biosynthesis. From these screens, we identified the alpha globin transcription factor, TFCP2, as a top hit. To investigate the role of TFCP2 in HS assembly, we targeted TFCP2 expression in human melanoma cells using the CRISPR/Cas9 system. TFCP2 knockout cells exhibited decreased fibroblast growth factor binding to cell surface HS, alterations in HS composition, and slowed cell growth compared to wildtype cells. Additionally, RNA sequencing revealed that TFCP2 regulates expression of multiple enzymes involved in HS assembly, including the secreted endosulfatase, SULF1. Pharmacological targeting of TFCP2 activity similarly reduced growth factor binding and increased SULF1 expression, and knockdown of SULF1 expression in TFCP2 mutant cells restored melanoma cell growth. Overall, these studies identify TFCP2 as a novel transcriptional regulator of HS and highlight HS-protein interactions as a possible target to slow melanoma growth.

2023-05-01 | GSE224599 | GEO

Fibroblast-specific reduction of heparan sulfate suppresses colon tumor growth and pancreatic cancer growth in mice

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-13 | GSE203602 | GEO

Effect of Continuous Suppression of Heparan Sulfate during Flow on Arterial Endothelial Function

Project description:The arterial endothelium’s response to its flow environment is critical to vascular homeostasis. The endothelial glycocalyx has been shown to play a major role in mechanotransduction, but the extent to which the components of the glycocalyx affect the overall function of the endothelium remains unclear. The objective of this study was to further elucidate the role of heparan sulfate as a mechanosensor on the surface of the arterial endothelium, by (1) expanding the variety of shear waveforms investigated, (2) continuously suppressing heparan sulfate expression rather than using a pre-flow batch treatment, and (3) performing microarray analysis on post-flow samples. Porcine aortic endothelial cells were exposed to non-reversing, reversing, and oscillatory shear waveforms for 24 hours with or without continuous heparan sulfate suppression with heparinase. All shear waveforms significantly increased the amount of heparan sulfate on the surface of the endothelium. Suppression of heparan sulfate to less than 25% of control levels did not inhibit shear-induced cell alignment or nitric oxide production, or alter gene expression, for any of the shear waveforms investigated. We infer that heparan sulfate on the surface of porcine aortic endothelial cells is not the primary mechanosensor for many shear-responsive endothelial cell functions in this species. Porcine aortic endothelial cells were exposed to 3 different shear waveforms for 24 hours with or without the addition of 300 mU/ml heparinase III to the flow media. The shear waveforms inculded Non-reversing (15 ± 15 dyne/cm2, 1 Hz), Steady (15 dyne/cm2), or Oscillatory (0 ± 15 dyne/cm2, 1 Hz) shear. Four replicates of each condition were performed for a total of 24 experiments. Each experimental sample was hybridized to an oligonucleotide array along with a standard reference sample (static cells).

2011-07-21 | E-GEOD-30843 | biostudies-arrayexpress

A genome-wide CRISPR/Cas9 screen reveals KDM2B as a modifier of protein binding to heparan sulfate

Project description:Heparan sulfate proteoglycans (HSPGs) are expressed on virtually all animal cells and are involved in many important biological processes. Each HSPG consists of a core protein with one or more covalently attached linear heparan sulfate (HS) chains composed of alternating glucosamine and uronic acids that are heterogeneously N- and O-sulfated. The arrangement and orientation of the sulfated sugar residues of HS specify the location of distinct ligand binding sites on the cell surface, and these modifications can vary temporally during development and spatially across tissues. While most of the enzymes involved in HS biosynthesis have been studied extensively, much less information exists regarding the specific mechanisms that give rise to the variable composition and binding properties of HS.

2021-01-28 | GSE163162 | GEO

A genome-wide CRISPR/Cas9 screen reveals KDM2B as a modifier of protein binding to heparan sulfate

2021-01-28 | GSE145789 | GEO

RNA analysis of Sox7- and Sox17-deficient mouse endothelial cells from high grade glioma

Project description:Glioblastoma multiforme (GBM) is a highly aggressive and vascularized malignant brain tumor. SoxF transcription factors consisting of Sox7, Sox17, and Sox18 are expressed specifically in endothelial cells (ECs) and contribute to vascular morphogenesis. While the role of Sox17 was found in subcutaneous ectopic tumors, Sox7 has not been studied in the context of tumor angiogenesis. Here, we investigated gene expression profile of RNA analysis of Sox7- and Sox17-deficient mouse endothelial cells from high grade glioma using RNA sequencing to validate molecular characteristics of Sox7 and Sox17 in high grade glioma.

2018-01-27 | GSE107530 | GEO

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