The role of heparan sulphate in development: the ectodermal story

Coulson‐Thomas, Vivien Jane

doi:10.1111/iep.12180

Cited by 22 publications

(13 citation statements)

References 178 publications

(329 reference statements)

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“…Heparan sulfate proteoglycans (HSPGs) carrying HS polysaccharide chains form the structure of ECM, participate in the cell-cell and cell-matrix interactions, and ensure migration activity of the cells and their binding to various growth factors and cytokines [ 9 , 10 , 11 ]. In the nervous system, HS interacts with a variety of physiologically important macromolecules, and plays a significant role in brain development and normal functioning, while undergoing changes during malignant transformation [ 12 , 13 , 14 ]. Different glioblastoma primary cell cultures have been shown to possess a high heterogeneity of the HS structure and composition, which has been associated with the adhesive properties and invasive activity of these cells [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation

Ushakov

Tsidulko

Bourdonnaye

et al. 2017

IJMS

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Heparan sulfate (HS) is an important component of the extracellular matrix and cell surface, which plays a key role in cell–cell and cell–matrix interactions. Functional activity of HS directly depends on its structure, which determined by a complex system of HS biosynthetic enzymes. During malignant transformation, the system can undergo significant changes, but for glioma, HS biosynthesis has not been studied in detail. In this study, we performed a comparative analysis of the HS biosynthetic system in human gliomas of different grades. RT-PCR analysis showed that the overall transcriptional activity of the main HS biosynthesis-involved genes (EXT1, EXT2, NDST1, NDST2, GLCE, HS2ST1, HS3ST1, HS3ST2, HS6ST1, HS6ST2, SULF1, SULF2, HPSE) was decreased by 1.5–2-fold in Grade II-III glioma (p < 0.01) and by 3-fold in Grade IV glioma (glioblastoma multiforme, GBM) (p < 0.05), as compared with the para-tumourous tissue. The inhibition was mainly due to the elongation (a decrease in EXT1/2 expression by 3–4-fold) and 6-O-sulfation steps (a decrease in 6OST1/2 expression by 2–5-fold) of the HS biosynthesis. Heparanase (HPSE) expression was identified in 50% of GBM tumours by immunostaining, and was characterised by a high intratumoural heterogeneity of the presence of the HPSE protein. The detected disorganisation of the HS biosynthetic system in gliomas might be a potential molecular mechanism for the changes of HS structure and content in tumour microenvironments, contributing to the invasion of glioma cells and the development of the disease.

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Section: Introductionmentioning

confidence: 99%

Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation

Ushakov

Tsidulko

Bourdonnaye

et al. 2017

IJMS

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“…HSPGs are involved in the development of the basement membrane barrier, providing a framework for epithelial support, regulating transport of solutes, and promoting the extravasation of cells during inflammatory responses [ 23 , 25 , 26 , 27 ]. HSPGs that are located at the cell surface are also involved in the establishment of morphogen and chemokine gradients important in WBC extravasation, but are also vital during development [ 28 , 29 , 30 ]. HSPGs located within secretory vesicles are involved in the packaging of vesicular contents, maintenance of protease activity, and regulating various activities upon secretion, such as host defense mechanisms and wound repair (e.g., [ 22 , 31 , 32 , 33 ]).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers

Hull

Montgomery

Leyva

2017

IJMS

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Emerging evidence suggests that the enzymes in the biosynthetic pathway for the synthesis of heparan sulfate moieties of heparan sulfate proteoglycans (HSPGs) are epigenetically regulated at many levels. As the exact composition of the heparan sulfate portion of the resulting HSPG molecules is critical to the broad spectrum of biological processes involved in oncogenesis, the epigenetic regulation of heparan sulfate biosynthesis has far-reaching effects on many cellular activities related to cancer progression. Given the current focus on developing new anti-cancer therapeutics focused on epigenetic targets, it is important to understand the effects that these emerging therapeutics may have on the synthesis of HSPGs as alterations in HSPG composition may have profound and unanticipated effects. As an introduction, this review will briefly summarize the variety of important roles which HSPGs play in a wide-spectrum of cancer-related cellular and physiological functions and then describe the biosynthesis of the heparan sulfate chains of HSPGs, including how alterations observed in cancer cells serve as potential biomarkers. This review will then focus on detailing the multiple levels of epigenetic regulation of the enzymes in the heparan sulfate synthesis pathway with a particular focus on regulation by miRNA and effects of epigenetic therapies on HSPGs. We will also explore the use of lectins to detect differences in heparan sulfate composition and preview their potential diagnostic and prognostic use in the clinic.

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“…GAG accumulation in lysosomes also interferes with the function of lysosomes as end‐station of the endocytic and autophagocytic transport pathways (Oussoren et al, ). GAG accumulation disrupts every system in the body, including bone, cartilage, and tooth development, because GAGs have crucial roles in regulatory functions involving the FGF, BMP, TGF‐β, and WNT signaling pathways in tooth, endochondral, and membranous bone ossification (Coulson‐Thomas, ; Pan et al, ; van der Eerden, Karperien, & Wit, ). Lysosomal GAG storage in chondrocytes disrupts the growth and maintenance of cartilage (Peck et al, ).…”

Section: Discussionmentioning

confidence: 99%

Oral manifestations in patients and dogs with mucopolysaccharidosis Type VII

Kantaputra

Smith

Casal

et al. 2019

American J of Med Genetics Pt A

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Mucopolysaccharidosis Type VII (MPS7, also called β-glucuronidase deficiency or Sly syndrome; MIM 253220) is an extremely rare autosomal recessive lysosomal storage disease, caused by mutations in the GUSB gene. β-glucuronidase (GUSB) is a lysosomal hydrolase involved in the stepwise degradation of glucuronic acid-containing glycosaminoglycans (GAGs). Patients affected with MPS VII are not able to completely degrade glucuronic acid-containing GAGs, including chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and heparan sulfate. The accumulation of these GAGs in lysosomes of various tissues leads to cellular and organ dysfunctions. Characteristic features of MPS VII include short stature, macrocephaly, hirsutism, coarse facies, hearing loss, cloudy cornea, short neck, valvular cardiac defects, hepatosplenomegaly, and dysostosis multiplex. Oral manifestations in patients affected with MPS VII have never been reported. Oral manifestations observed in three patients consist of wide root canal spaces, taurodontism, hyperplastic dental folli-cles, malposition of unerupted permanent molars, and failure of tooth eruption with malformed roots. The unusual skeletal features of the patients include maxillary hypoplasia, hypoplastic midface, long mandibular length, mandibular prognathism, hypoplastic and aplastic mandibular condyles, absence of the dens of the second cervical vertebra, and erosion of the cortex of the lower border of mandibles. Dogs affected with MPS VII had anterior and posterior open bite, maxillary hypoplasia, premolar crowding, and mandibular prognathism. Unlike patients with MPS VII, the dogs had

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The role of heparan sulphate in development: the ectodermal story

Cited by 22 publications

References 178 publications

Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation

Heparan Sulfate Biosynthetic System Is Inhibited in Human Glioma Due to EXT1/2 and HS6ST1/2 Down-Regulation

Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers

Oral manifestations in patients and dogs with mucopolysaccharidosis Type VII

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