Tumor Acidosis Remodels the Glycocalyx to Control Lipid Scavenging and Ferroptosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE300142 | GEO | 2026/01/05
REPOSITORIES: GEO
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Project description:In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors. We used microarrays to evaluate transcriptional signature realted lipid droplet (LD)+ and LD- regions of patient glioblastoma (GBM) sections.
2026-01-04 | GSE300758 | GEO
Project description:In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors. We used microarrays to evaluate transcriptional signature realted to 3D (LD⁺) cultures compared to 2D (LD⁻) cultures from primary glioblastoma (GBM) cell line.
2026-01-04 | GSE300771 | GEO
Project description:In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors. We used microarrays to evaluate transcriptional signature of acidosis adaptation, short-term acidosis (pH 6.4) or short-term hypoxia in U87MG GBM cells.
2026-01-04 | GSE300765 | GEO
Project description:In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors. We used microarrays to evaluate transcriptional signature of adaptation to acidosis (pH 6.4) in PANC1 pancreatic cancer cells.
2026-01-04 | GSE300768 | GEO
Project description:Infiltration of peripheral immune cells after blood-brain barrier (BBB) dysfunction causes severe inflammation after a stroke. Although the endothelial glycocalyx functions as a barrier to circulating cells, the relationship between stroke severity and glycocalyx dysfunction remains unclear. In this study, glycosaminoglycans (GAGs), a component of the endothelial glycocalyx, in ischemic stroke were studied using a photochemically induced thrombosis (PIT) mouse model. As results, decreased levels of heparan sulfate (HS) and chondroitin sulfate (CS) and increased activity of hyaluronidase 1 and heparanase (HPSE) were observed in ischemic brain tissues. HPSE expression in cerebral vessels increased after stroke onset and infarct volume greatly decreased after co-administration of N-acetylcysteine (NAC)+GAG oligosaccharides as compared to NAC administration alone. These results suggest that the endothelial glycocalyx was injured after the onset of stroke. Interestingly, scission activity of proHPSE produced by HBMEC/ciβ and HEK293 cells transfected with hHPSE1 cDNA were activated by acrolein exposure. We identified the ACR modified amino acid residues of proHPSE using nano LC-MS/MS, suggesting that ACR modification of Lys139 (6-kDa linker), and Lys107 and Lys161, located in the immediate vicinity of the 6-kDa linker, at least in part, is attributed to the activation of proHPSE. Since proHPSE, but not HPSE, localizes outside cells by binding with HS proteoglycans, ACR-modified proHPSE represents a promising target to protect the endothelial glycocalyx.
2020-11-16 | PXD021040 | Pride
Project description:Giantsos-Adams2013 - Growth of glycocalyx
under static conditions
This model is described in the article:
Heparan Sulfate Regrowth
Profiles Under Laminar Shear Flow Following Enzymatic
Degradation.
Giantsos-Adams KM, Koo AJ, Song S,
Sakai J, Sankaran J, Shin JH, Garcia-Cardena G, Dewey CF.
Cell Mol Bioeng 2013 Jun; 6(2):
160-174
Abstract:
The local hemodynamic shear stress waveforms present in an
artery dictate the endothelial cell phenotype. The observed
decrease of the apical glycocalyx layer on the endothelium in
atheroprone regions of the circulation suggests that the
glycocalyx may have a central role in determining
atherosclerotic plaque formation. However, the kinetics for the
cells' ability to adapt its glycocalyx to the environment have
not been quantitatively resolved. Here we report that the
heparan sulfate component of the glycocalyx of HUVECs increases
by 1.4-fold following the onset of high shear stress, compared
to static cultured cells, with a time constant of 19 h.
Cell morphology experiments show that 12 h are required
for the cells to elongate, but only after 36 h have the
cells reached maximal alignment to the flow vector. Our
findings demonstrate that following enzymatic degradation,
heparan sulfate is restored to the cell surface within
12 h under flow whereas the time required is 20 h
under static conditions. We also propose a model describing the
contribution of endocytosis and exocytosis to apical heparan
sulfate expression. The change in HS regrowth kinetics from
static to high-shear EC phenotype implies a differential in the
rate of endocytic and exocytic membrane turnover.
This model is hosted on
BioModels Database
and identified by:
MODEL1609100001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
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 | BIOMD0000000830 | BioModels
Project description:Giantsos-Adams2013 - Growth of glycocalyx
under static conditions
This model is described in the article:
Heparan Sulfate Regrowth
Profiles Under Laminar Shear Flow Following Enzymatic
Degradation.
Giantsos-Adams KM, Koo AJ, Song S,
Sakai J, Sankaran J, Shin JH, Garcia-Cardena G, Dewey CF.
Cell Mol Bioeng 2013 Jun; 6(2):
160-174
Abstract:
The local hemodynamic shear stress waveforms present in an
artery dictate the endothelial cell phenotype. The observed
decrease of the apical glycocalyx layer on the endothelium in
atheroprone regions of the circulation suggests that the
glycocalyx may have a central role in determining
atherosclerotic plaque formation. However, the kinetics for the
cells' ability to adapt its glycocalyx to the environment have
not been quantitatively resolved. Here we report that the
heparan sulfate component of the glycocalyx of HUVECs increases
by 1.4-fold following the onset of high shear stress, compared
to static cultured cells, with a time constant of 19 h.
Cell morphology experiments show that 12 h are required
for the cells to elongate, but only after 36 h have the
cells reached maximal alignment to the flow vector. Our
findings demonstrate that following enzymatic degradation,
heparan sulfate is restored to the cell surface within
12 h under flow whereas the time required is 20 h
under static conditions. We also propose a model describing the
contribution of endocytosis and exocytosis to apical heparan
sulfate expression. The change in HS regrowth kinetics from
static to high-shear EC phenotype implies a differential in the
rate of endocytic and exocytic membrane turnover.
This model is hosted on
BioModels Database
and identified by:
MODEL1609100001.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
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.
2016-09-28 | MODEL1609100001 | BioModels
Project description:Sepsis patients are at increased risk for hospital-acquired pulmonary infections, potentially due to post-septic immunosuppression known as the compensatory anti-inflammatory response syndrome (CARS). CARS has been attributed to leukocyte dysfunction, with an unclear role for endothelial cells. The pulmonary circulation is lined by an endothelial glycocalyx, a heparan sulfate-rich layer essential to pulmonary homeostasis. Heparan sulfate degradation occurs early in sepsis, leading to lung injury. Endothelial synthesis of new heparan sulfates subsequently allows for glycocalyx reconstitution and endothelial recovery. We hypothesized that remodeling of the reconstituted endothelial glycocalyx, mediated by alterations in the endothelial machinery responsible for heparan sulfate synthesis, contributes to CARS. Our experimental animal model of CARS recapitulated post-septic immunosuppression, coincidentally with structural remodeling of endothelial glycocalyx heparan sulfate. We used microarray to identify which heparan sulfate modifying enzyme is responsible for the remodeling of post-septic reconstituted glycocalyx, characterized with enrichment of heparan sulfate disaccharides sulfated at the 6-O position of glucosamine.
2019-04-14 | GSE129775 | GEO
Project description:The skin barrier consists of multiple lipid-enriched layers. Sodium lauryl sulfate is a well-known substance that can disrupt the skin barrier. The mechanisms underlying the barrier repair process, especially the influence of topical sodium lauryl sulfate treatment in the barrier recovery phase remain unresolved. To understand the process of reconstruction of the intercellular lipid layer of the skin after acute barrier disruption by sodium lauryl sulfate treatment in vivo.
2023-01-01 | GSE146969 | GEO
Project description:Glioblastoma (GBM) is the most common and malignant primary brain tumor. The extracellular matrix (ECM), also known as the matrisome, helps determine glioma invasion, adhesion, and growth. Little attention, however, has been paid to glycosylation of the ECM components that constitute the majority of glycosylated protein mass and presumed biological properties. To acquire a comprehensive understanding of the biological functions of the matrisome and its components, including proteoglycans and glycosaminoglycans (GAGs), in GBM tumorigenesis, and to identify potential biomarker candidates, we studied the alterations of GAGs, including heparan sulfate (HS) and chondroitin sulfate (CS), the core proteins of proteoglycans, and other glycosylated matrisomal proteins in GBM subtypes vs. control human brain tissue samples. We scrutinized the proteomics data to acquire in-depth site-specific glycoproteomic profiles of the GBM subtypes that will assist in identifying specific glycosylation changes in GBM. We observed an increase in CS 6-O sulfation and a decrease in HS 6-O sulfation, accompanied by an increase in unsulfated CS and HS disaccharides in GBM vs. control samples. Several core matrisome proteins, including proteoglycans (decorin, biglycan, agrin, prolargin, glypican-1, CSPG4), tenascin, fibronectin, hyaluronan link protein 1 and 2, laminins, and collagens, were differentially regulated in GBM vs. controls. Interestingly, a higher degree of collagen hydroxyprolination was also observed for GBM vs. controls. Further, two proteoglycans, CSPG4 and agrin, were significantly lower, about 6–fold for IDH-mutant compared to the WT GBM samples. Differential regulation of O-glycopeptides for proteoglycans, including brevican, neurocan, and versican, was observed for GBM subtypes vs. controls. Moreover, an increase in levels of glycosyltransferase and glycosidase enzymes was observed for GBM when compared to control samples. We also report distinct protein, peptide, and glycopeptide features for GBM subtypes comparisons. Taken together, our study informs understanding of the alterations to key matrisomal molecules that occur during GBM development.
2022-04-04 | PXD028931 | Pride