G-Protein Coupled Receptor 124 (GPR124) in Endothelial Cells Regulates Vascular Endothelial Growth Factor (VEGF)-Induced Tumor Angiogenesis

Wang, YaoHui; Cho, S.-G.; Wu, Xu; Siwko, Stefan; Liu, M.

doi:10.2174/1566524014666140414205943

Cited by 29 publications

(19 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reck associates with Gpr124, another novel member of the canonical Wnt signaling pathway that acts downstream of Wnt7 ligands, which has a role in cerebrovascular and DRG development similar to Reck (Posokhova et al, 2015;Vanhollebeke et al, 2015;Wang et al, 2014;. Thus, Reck-Gpr124 heteromers might modulate Wnt7 binding, the assembly of the Wnt signaling complex, its internalization and/or MP-mediated processing events that gate its activity.…”

Section: Discussionmentioning

confidence: 99%

Reck enables cerebrovascular development by promoting canonical Wnt signaling

et al. 2015

View full text Add to dashboard Cite

The cerebral vasculature provides the massive blood supply that the brain needs to grow and survive. By acquiring distinctive cellular and molecular characteristics it becomes the blood-brain barrier (BBB), a selectively permeable and protective interface between the brain and the peripheral circulation that maintains the extracellular milieu permissive for neuronal activity. Accordingly, there is great interest in uncovering the mechanisms that modulate the formation and differentiation of the brain vasculature. By performing a forward genetic screen in zebrafish we isolated no food for thought (nft y72 ), a recessive late-lethal mutant that lacks most of the intracerebral central arteries (CtAs), but not other brain blood vessels. We found that the cerebral vascularization deficit of nft y72 mutants is caused by an inactivating lesion in reversion-inducing cysteine-rich protein with Kazal motifs [reck; also known as suppressor of tumorigenicity 15 protein (ST15)], which encodes a membrane-anchored tumor suppressor glycoprotein. Our findings highlight Reck as a novel and pivotal modulator of the canonical Wnt signaling pathway that acts in endothelial cells to enable intracerebral vascularization and proper expression of molecular markers associated with BBB formation. Additional studies with cultured endothelial cells suggest that, in other contexts, Reck impacts vascular biology via the vascular endothelial growth factor (VEGF) cascade. Together, our findings have broad implications for both vascular and cancer biology.

show abstract

Section: Discussionmentioning

confidence: 99%

Reck enables cerebrovascular development by promoting canonical Wnt signaling

et al. 2015

View full text Add to dashboard Cite

show abstract

“…We cross‐validated the RNA‐seq data from each functional category in AhR −/− and wt mouse RPE‐choroid samples using qPCR (Figure B); primers are listed in Table S3 (see supplementary material). We observed down‐regulation of Gpr124 , a regulator of angiogenesis also known as tumour endothelial factor 5 , down‐regulation of the ECM gene collagen type V α 1 ( Col5a1 ) and up‐regulation of the inflammatory gene chemokine (C–C motif) receptor 1 ( Ccr1 ) . These genes displayed a significant fold change, the direction and magnitude of which was consistent with the RNA‐seq analysis.…”

Section: Resultsmentioning

confidence: 99%

Aryl hydrocarbon receptor knock‐out exacerbates choroidal neovascularization via multiple pathogenic pathways

Choudhary

Kazmin

et al. 2014

The Journal of Pathology

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR−/− and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR−/− mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1+) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C–C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that are consistent with a possible role of AhR in wet AMD. The data discussed in this paper have been deposited in NCBI's Gene Expression Omnibus; GEO Submission No. GSE56983, NCBI Tracking System No. 17021116.

show abstract

“…Mouse xenograft tumor angiogenic vessels formation and in turn tumor growth were inhibited by silencing TEM5 in human endothelial cells. TEM5 regulated VEGF-induced tumor angiogenic processes in vitro including cell-cell interaction, permeability, migration, invasion, and tube formation [74]. In vitro study showed that knockdown of TEM5 in non-small cell lung cancer (NSCLC) reduces resistance to gefitinib [75].…”

Section: Tumor Endothelial Markers (Tems)mentioning

confidence: 99%

Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

Pietrzyk

2016

Disease Markers

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs) are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients.

show abstract

G-Protein Coupled Receptor 124 (GPR124) in Endothelial Cells Regulates Vascular Endothelial Growth Factor (VEGF)-Induced Tumor Angiogenesis

Cited by 29 publications

References 0 publications

Reck enables cerebrovascular development by promoting canonical Wnt signaling

Reck enables cerebrovascular development by promoting canonical Wnt signaling

Aryl hydrocarbon receptor knock‐out exacerbates choroidal neovascularization via multiple pathogenic pathways

Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

Contact Info

Product

Resources

About