Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes

Su, Zhendong; Kishida, Satoshi; Tsubota, Shoma; Sakamoto, Kazunari; Cao, Dongliang; Kiyonari, Shinichi; Ohira, Miki; Narita, Atsushi; Xu, Yinyan; Takahashi, Yoshiyuki

doi:10.18632/oncotarget.22435

Cited by 33 publications

(27 citation statements)

References 34 publications

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“…As mentioned previously, HSPGs promote the differentiation of neuroblasts, while surface expression of HSPGs and release of soluble forms from the stroma promote FGF2 signaling, which suppresses proliferation in neuroblastoma . Recently, it was reported that NCAN is highly expressed in neuroblastoma and induces an undifferentiated status and stimulates cell division, thereby promoting the malignancy of neuroblastoma cells by providing a growth advantage .…”

Section: Brain Pathogenesismentioning

confidence: 85%

Proteoglycans in brain development and pathogenesis

Schwartz

Domowicz

2018

FEBS Letters

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Edited by Sandro SonninoProteoglycans are diverse, complex extracellular/cell surface macromolecules composed of a central core protein with covalently linked glycosaminoglycan (GAG) chains; both of these components contribute to the growing list of important bio-active functions attributed to proteoglycans. Increasingly, attention has been paid to the roles of proteoglycans in nervous tissue development due to their highly regulated spatio/temporal expression patterns, whereby they promote/inhibit neurite outgrowth, participate in specification and maturation of various precursor cell types, and regulate cell behaviors like migration, axonal pathfinding, synaptogenesis and plasticity. These functions emanate from both the environments proteoglycans create around cells by retaining ions and water or serving as scaffolds for cell shaping or motility, and from dynamic interactions that modulate signaling fields for cytokines, growth factors and morphogens, which may bind to either the protein or GAG portions. Also, genetic abnormalities impacting proteoglycan synthesis during critical steps of brain development and response to environmental insults and injuries, as well as changes in microenvironment interactions leading to tumors in the central nervous system, all suggest roles for proteoglycans in behavioral and intellectual disorders and malignancies.Keywords: central nervous system; chondroitin sulfate; extracellular matrix; glycosaminoglycans; heparan sulfate; Proteoglycans; proteoglycaninteracting molecules Understanding the structure/function relationships, modes of interaction, spatial/temporal expression patterns, and functional roles of neural proteoglycans during brain development is essential for a full appreciation of the contributions of proteoglycans to establishment and maintenance of the nervous system. Increasingly, proteoglycans are implicated in developmental plasticity, recovery from injury, genetically induced defects that lead to intellectual disorders, and altered micro-environments that induce tumorigenesis. Lastly, promising new avenues of research exploration suggest proteoglycans may serve as biomarkers of disease and/or targets for therapy. Each of these areas is summarized in this review, highlighting how the modulation of proteoglycan structure promotes their ability to interact with diverse partners, thus regulating basic processes like proliferation and differentiation that in turn profoundly influence normal development which can lead to pathological conditions. Abbreviations ACAN,aggrecan; ADAMTS, disintegrin and metalloproteinases with thrombospondin motifs; BBB, blood-brain barrier; BCAN, brevican; BDNF, brain-derived neurotrophic factor; CHPF, chondroitin polymerazing factor; CHSY, chondroitin sulfate synthase; CNS, central nervous system;

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Section: Brain Pathogenesismentioning

confidence: 85%

Proteoglycans in brain development and pathogenesis

Schwartz

Domowicz

2018

FEBS Letters

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“…In response to hypoxia, high glucose, and inflammation conditions, multiple signaling pathways are activated in these cells, which are involved in retinal remodeling following retinal damage [ 24 ]. Furthermore, high NCAN expression has been associated with unfavorable outcome in neuroblastoma, as it induces an undifferentiated phenotype that promotes the malignancy [ 25 ]. ATP6V1C1 belongs to the vacuolar (H+)-ATPases (or V-ATPases) family that is responsible for the acidification of intracellular compartments in eukaryotic cells [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding

Galardi

Colletti

Lavarello

et al. 2020

Cancers

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Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Although recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remains difficult in the presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes, membrane-derived nanovesicles that are secreted abundantly by aggressive tumor cells and that can be isolated from several biological fluids, represent an interesting alternative for the detection of tumor-associated biomarkers. In this study, we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosomes RBT and one RBVS group, respectively. Gene enrichment analysis of exclusively and differentially expressed proteins and network analysis identified in RBVS exosomes upregulated proteins specifically related to invasion and metastasis, such as proteins involved in extracellular matrix (ECM) remodeling and interaction, resistance to anoikis and the metabolism/catabolism of glucose and amino acids.

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“…Of the four genes, AHCY has been reported to be a direct target of MYCN , which predicts poor prognosis in NB ( Chayka et al, 2015 ). NCAN has been confirmed to promote the malignant phenotypes in NB cells ( Su et al, 2017 ). ERCC Excision Repair 6 Like ( ERCC6L , Spindle Assembly Checkpoint Helicase) is a protein-coding gene, also known as PICH, its related pathways include cell cycle and mitosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Prognostic Genes for Neuroblastoma

Zhong

Liu

et al. 2018

Front. Genet.

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Background and Objective: Neuroblastoma (NB), the most common pediatric solid tumor apart from brain tumor, is associated with dismal long-term survival. The aim of this study was to identify a gene signature to predict the prognosis of NB patients.Materials and Methods: GSE49710 dataset from the Gene Expression Omnibus (GEO) database was downloaded and differentially expressed genes (DEGs) were analyzed using R package “limma” and SPSS software. The gene ontology (GO) and pathway enrichment analysis were established via DAVID database. Random forest (RF) and risk score model were used to pick out the gene signature in predicting the prognosis of NB patients. Simultaneously, the receiving operating characteristic (ROC) and Kaplan-Meier curve were plotted. GSE45480 and GSE16476 datasets were employed to validate the robustness of the gene signature.Results: A total of 131 DEGs were identified, which were mainly enriched in cancer-related pathways. Four genes (ERCC6L, AHCY, STK33, and NCAN) were selected as a gene signature, which was included in the top six important features in RF model, to predict the prognosis in NB patients, its area under the curve (AUC) could reach 0.86, and Cox regression analysis revealed that the 4-gene signature was an independent prognostic factor of overall survival and event-free survival. As well as in GSE16476. Additionally, the robustness of discriminating different groups of the 4-gene signature was verified to have a commendable performance in GSE45480 and GSE49710.Conclusion: The present study identified a gene-signature in predicting the prognosis in NB, which may provide novel prognostic markers, and some of the genes may be as treatment targets according to biological experiments in the future.

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Neurocan, an extracellular chondroitin sulfate proteoglycan, stimulates neuroblastoma cells to promote malignant phenotypes

Cited by 33 publications

References 34 publications

Proteoglycans in brain development and pathogenesis

Proteoglycans in brain development and pathogenesis

Proteomic Profiling of Retinoblastoma-Derived Exosomes Reveals Potential Biomarkers of Vitreous Seeding

Identification of Potential Prognostic Genes for Neuroblastoma

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