Quantitatively relating brain endothelial cell–cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program

Gray, Kelsey M.; Jung, Jae Woo; Inglut, Collin T.; Huang, Huang‐Chiao; Stroka, Kimberly M.

doi:10.1186/s12987-020-0177-y

Cited by 18 publications

(26 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MMP-2 and MMP-9 represent the predominantly extracellularlyliberated isoforms implicated in enhancing invasion and metastasis by glioma cells [102]. Human brain microvascular endothelial cells (HBMECs) maintain the microarchitectural integrity of the blood brain barrier [103]. Treatment of HBMECs grown on collagen I, collagen IV, fibronectin, laminin, or hyaluronic acid with cyclic AMP supplements enhances microarchitectural junctional continuity and expression of zona occludin 1, VE-cadherin, and claudin 5 [103].…”

Section: Modulation Of Matrix Metalloproteinase Expression By β Adrenmentioning

confidence: 99%

“…Human brain microvascular endothelial cells (HBMECs) maintain the microarchitectural integrity of the blood brain barrier [103]. Treatment of HBMECs grown on collagen I, collagen IV, fibronectin, laminin, or hyaluronic acid with cyclic AMP supplements enhances microarchitectural junctional continuity and expression of zona occludin 1, VE-cadherin, and claudin 5 [103]. Inhibition of MMP-9 effectively forestalls HBMEC neoangiogenesis [104], invasiveness [104], and metastasis [105] in vitro.…”

Section: Modulation Of Matrix Metalloproteinase Expression By β Adrenmentioning

confidence: 99%

See 1 more Smart Citation

RETRACTED ARTICLE: β adrenergic receptor modulated signaling in glioma models: promoting β adrenergic receptor-β arrestin scaffold-mediated activation of extracellular-regulated kinase 1/2 may prove to be a panacea in the treatment of intracranial and spinal malignancy and extra-neuraxial carcinoma

Ghali

2020

Mol Biol Rep

View full text Add to dashboard Cite

Neoplastically transformed astrocytes express functionally active cell surface β adrenergic receptors (βARs). Treatment of glioma models in vitro and in vivo with β adrenergic agonists variably amplifies or attenuates cellular proliferation. In the majority of in vivo models, β adrenergic agonists generally reduce cellular proliferation. However, treatment with β adrenergic agonists consistently reduces tumor cell invasive potential, angiogenesis, and metastasis. β adrenergic agonists induced decreases of invasive potential are chiefly mediated through reductions in the expression of matrix metalloproteinases types 2 and 9. Treatment with β adrenergic agonists also clearly reduce tumoral neoangiogenesis, which may represent a putatively useful mechanism to adjuvantly amplify the effects of bevacizumab. Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor. We may accordingly designate βagonists to represent an enhancer of bevacizumab. The antiangiogenic effects of β adrenergic agonists may thus effectively render an otherwise borderline effective therapy to generate significant enhancement in clinical outcomes. β adrenergic agonists upregulate expression of the major histocompatibility class II DR alpha gene, effectively potentiating the immunogenicity of tumor cells to tumor surveillance mechanisms. Authors have also demonstrated crossmodal modulation of signaling events downstream from the β adrenergic cell surface receptor and microtubular polymerization and depolymerization. Complex effects and desensitization mechanisms of the β adrenergic signaling may putatively represent promising therapeutic targets. Constant stimulation of the β adrenergic receptor induces its phosphorylation by β adrenergic receptor kinase (βARK), rendering it a suitable substrate for alternate binding by β arrestins 1 or 2. The binding of a β arrestin to βARK phosphorylated βAR promotes receptor mediated internalization and downregulation of cell surface receptor and contemporaneously generates a cell surface scaffold at the βAR. The scaffold mediated activation of extracellular regulated kinase 1/2, compared with protein kinase A mediated activation, preferentially favors cytosolic retention of ERK1/2 and blunting of nuclear translocation and ensuant pro-transcriptional activity. Thus, βAR desensitization and consequent scaffold assembly effectively retains the cytosolic homeostatic functions of ERK1/2 while inhibiting its pro-proliferative effects. We suggest these mechanisms specifically will prove quite promising in developing primary and adjuvant therapies mitigating glioma growth, angiogenesis, invasive potential, and angiogenesis. We suggest generating compounds and targeted mutations of the β adrenergic receptor favoring β arrestin binding and scaffold facilitated activation of ERK1/2 may hold potential promise and therapeutic benefit in adjuvantly treating most or all cancers. We hope our discussion will generate fruitful research endeavors seeking to exploit these mechanisms.

show abstract

Section: Modulation Of Matrix Metalloproteinase Expression By β Adrenmentioning

confidence: 99%

Section: Modulation Of Matrix Metalloproteinase Expression By β Adrenmentioning

confidence: 99%

RETRACTED ARTICLE: β adrenergic receptor modulated signaling in glioma models: promoting β adrenergic receptor-β arrestin scaffold-mediated activation of extracellular-regulated kinase 1/2 may prove to be a panacea in the treatment of intracranial and spinal malignancy and extra-neuraxial carcinoma

Ghali

2020

Mol Biol Rep

View full text Add to dashboard Cite

show abstract

“…Another important consideration in a 2D model is the ECM coating used on the membrane to mimic the microenvironment of the human brain basement membrane. Recent studies have explored the effect of ECM composition on endothelial cell tight junction properties [ 34 ], as well as permeability in Transwell inserts [ 35 ]. However, there are limited investigations into ECM coatings appropriate for coculture and tricultures in 2D environments that incorporate flow.…”

Section: Boc Developmentmentioning

confidence: 99%

“…However, the limited availability of human cerebral tissue makes cell sourcing challenging and introduces between-donor variabilities. Further, primary HBMECs also do not achieve physiological TEER, even under various optimized culture conditions [ 12 , 34 , 74 ]. Another major concern for primary cells is their dedifferentiation in vitro, which has been well-documented by many groups [ 81 , 83 ].…”

Section: Decision Workflow: Factors To Consider When Selecting a Model Systemmentioning

confidence: 99%

“…Additionally, replication of brain homeostasis can be optimized using growth factors and additional proteins in the media or hydrogel environment. Astrocyte conditioned media containing cyclic adenosine monophosphate (cAMP) or the addition of Rho-associated kinase (ROCK) inhibitor combined with cAMP has been shown to facilitate a more BBB-like monolayer in HUVECs [ 299 ], primary HBMECs [ 34 ] and iPSC-derived BMECs [ 35 ].…”

Section: Decision Workflow: Factors To Consider When Selecting a Model Systemmentioning

confidence: 99%

See 1 more Smart Citation

Review of Design Considerations for Brain-on-a-Chip Models

et al. 2021

View full text Add to dashboard Cite

In recent years, the need for sophisticated human in vitro models for integrative biology has motivated the development of organ-on-a-chip platforms. Organ-on-a-chip devices are engineered to mimic the mechanical, biochemical and physiological properties of human organs; however, there are many important considerations when selecting or designing an appropriate device for investigating a specific scientific question. Building microfluidic Brain-on-a-Chip (BoC) models from the ground-up will allow for research questions to be answered more thoroughly in the brain research field, but the design of these devices requires several choices to be made throughout the design development phase. These considerations include the cell types, extracellular matrix (ECM) material(s), and perfusion/flow considerations. Choices made early in the design cycle will dictate the limitations of the device and influence the end-point results such as the permeability of the endothelial cell monolayer, and the expression of cell type-specific markers. To better understand why the engineering aspects of a microfluidic BoC need to be influenced by the desired biological environment, recent progress in microfluidic BoC technology is compared. This review focuses on perfusable blood–brain barrier (BBB) and neurovascular unit (NVU) models with discussions about the chip architecture, the ECM used, and how they relate to the in vivo human brain. With increased knowledge on how to make informed choices when selecting or designing BoC models, the scientific community will benefit from shorter development phases and platforms curated for their application.

show abstract

A novel mitochondria-related gene signature in esophageal carcinoma: prognostic, immune, and therapeutic features

Zhang

Niu

et al. 2023

Funct Integr Genomics

View full text Add to dashboard Cite

Esophageal Carcinoma (ESCA) is a common and lethal malignant tumor worldwide. A role for mitochondria in tumorigenesis and progression has been proposed. The mitochondrial biomarkers were useful in nding signi cant prognostic gene modules associated with ESCA. In the present work, we obtained the transcriptome expression pro les and corresponding clinical information of ESCA from The Cancer Genome Atlas (TCGA). Differential expressed genes (DEGs) were overlapped with mitochondria related genes to obtain mitochondria related DEGs. The univariate cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and multivariate cox regression was sequentially used to de ne the risk scoring model for mitochondria-related DEGs, and its prognostic value was veri ed in the external datasets GSE53624. Based on risk score, ESCA patients were divided into high and low risk groups. GO, KEGG and Gene Set Enrichment Analysis (GSEA) were performed to further investigate the difference between low and high risk groups in the gene pathway level. CIBERSORT was used to evaluate immune cell in ltration. The mutation difference between high and low risk groups was compared by the R package "Maftools". Cellminer was used to assess the interactions of the risk scoring model and drug sensitivity. As the most important outcome of the study, we obtained 306 mitochondria related DEGs, and constructed a 6-gene risk scoring model (APOOL, HIGD1A, MAOB, BCAP31, SLC44A2 and CHPT1). Between high and low risk group, pathways including "hippo signaling pathway" and "cell-cell junction" was enriched. According to CIBERSORT, samples with high risk demonstrated higher abundance of CD4 + T cells, NK cells, M0 and M2 Macrophages, and lower abundance of M1 Macrophages. The immune cell marker genes were correlated with risk score. In mutation analysis, the mutation rate of TP53 was signi cantly different between the high and low risk groups. Drugs with strong correlation with model genes and risk score were selected. In conclusion, we focused on the role of mitochondria-related genes in cancer development, and proposed a prognostic signature for individualized integrative assessment.

show abstract

Quantitatively relating brain endothelial cell–cell junction phenotype to global and local barrier properties under varied culture conditions via the Junction Analyzer Program

Cited by 18 publications

References 67 publications

Review of Design Considerations for Brain-on-a-Chip Models

A novel mitochondria-related gene signature in esophageal carcinoma: prognostic, immune, and therapeutic features

Contact Info

Product

Resources

About