Mouse Testican-2

Schnepp, Anke; Lindgren, Patricia Komp; Hülsmann, Hanni; Kröger, Stephan; Paulsson, Mats; Hartmann, Ursula

doi:10.1074/jbc.m414276200

Cited by 56 publications

(41 citation statements)

References 26 publications

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“…Similarly, CYFIP2 has been shown to negatively modulate survival of colon cancer cells (37). Epigenetic inactivation of SPOCK2 gene is involved in malignant transformation of ovarian endometriosis (38,39). Interestingly, PYGO1 and BCL9L, hypermethylated in metastatic PPGL, participate in the nuclear b-catenin/TCF complex.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers

Cubas

Korpershoek

Inglada-Pérez

et al. 2015

Clinical Cancer Research

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Purpose: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors, associated with highly variable postoperative evolution. The scarcity of reliable PPGL prognostic markers continues to complicate patient management. In this study, we explored genome-wide DNA methylation patterns in the context of PPGL malignancy to identify novel prognostic markers.Experimental Design: We retrospectively investigated DNA methylation patterns in PPGL with and without metastases using high-throughput DNA methylation profiling data (Illumina 27K) from two large, well-characterized discovery (n ¼ 123; 24 metastatic) and primary validation (n ¼ 154; 24 metastatic) series. Additional validation of candidate CpGs was performed by bisulfite pyrosequencing in a second independent set of 33 paraffin-embedded PPGLs (19 metastatic).Results: Of the initial 86 candidate CpGs, we successfully replicated 52 (47 genes), associated with metastatic PPGL. Of these, 48 CpGs showed significant associations with time to progression even after correcting for SDHB genotype, suggesting their value as prognostic markers independent of genetic background. Hypermethylation of RDBP (negative elongation factor complex member E) in metastatic tumors was further validated by bisulfite pyrosequencing [Db metastatic-benign ¼ 0.29, P ¼ 0.003; HR, 1.4; 95% confidence interval (CI), 1.1-2.0; P ¼ 0.018] and may alter transcriptional networks involving (RERG, GPX3, and PDZK1) apoptosis, invasion, and maintenance of DNA integrity.Conclusions: This is the first large-scale study of DNA methylation in metastatic PPGL that identifies and validates prognostic markers, which could be used for stratifying patients according to risk of developing metastasis. Of the three CpGs selected for further validation, one (RDBP) was clearly confirmed and could be used for stratifying patients according to the risk of developing metastases. Clin Cancer Res; 21(13); 3020-30. Ó2015 AACR.

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Section: Discussionmentioning

confidence: 99%

DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers

Cubas

Korpershoek

Inglada-Pérez

et al. 2015

Clinical Cancer Research

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“…The NDRG2 gene is part of a fourmember gene family whose members are involved in cell differentiation, and NDRG2 has been shown to be expressed in the embryonic ventricular zone as well as in neurogenic regions in adult brain (Okuda and Kondoh, 1999). Also downregulated was sparc/ osteonectin, cwcv and kazal-like domains proteoglycan 2 (SPOCK2), an extracellular protein also known as testican-2, which has functions that include regulation of protease activity (Nakada et al, 2003) and neurite outgrowth (Schnepp et al, 2005). Finally, semaphorin 3G (SEMA3G) was also identified as being downregulated in BMEC cultures and while little is known about this semaphorin isoform, it has been shown to have involvement in axonal guidance through neuropilin-2 (Taniguchi et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

A Genomic Comparison of in vivo and in vitro Brain Microvascular Endothelial Cells

Calabria

Shusta

2007

J Cereb Blood Flow Metab

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The blood-brain barrier (BBB) is composed of uniquely differentiated brain microvascular endothelial cells (BMEC). Often, it is of interest to replicate these attributes in the form of an in vitro model, and such models are widely used in the research community. However, the BMEC used to create in vitro BBB models de-differentiate in culture and lose many specialized characteristics. These changes are poorly understood at a molecular level, and little is known regarding the consequences of removing BMEC from their local in vivo microenvironment. To address these issues, suppression subtractive hybridization (SSH) was used to identify 25 gene transcripts that were differentially expressed between in vivo and in vitro BMEC. Genes affected included those involved in angiogenesis, transport and neurogenesis, and real-time quantitative polymerase chain reaction (qPCR) verified transcripts were primarily and significantly downregulated. Since this quantitative gene panel represented those BMEC characteristics lost upon culture, we used it to assess how culture manipulation, specifically BMEC purification and barrier induction by hydrocortisone, influenced the quality of in vitro models. Puromycin purification of BMEC elicited minimal differences compared with untreated BMEC, as assessed by qPCR. In contrast, qPCR-based gene panel analysis after induction with hydrocortisone indicated a modest shift of 10 of the 23 genes toward a more 'in vivo-like' gene expression profile, which correlated with improved barrier phenotype. Genomic analysis of BMEC de-differentiation in culture has thus yielded a functionally diverse set of genes useful for comparing the in vitro and in vivo BBB.

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“…Interestingly, the initial screen of ES cells demonstrated that message was present for a wide variety of PG core proteins, including many that have been shown to have tightly regulated spatiotemporal distribution in vivo. These include HSPG syndecan 3 and chondroitin sulfate proteoglycans (CSPGs) testican [24] and leprecan [25]. However, the CSPG NG2, often used as a neural-specific marker [26], was found only in the day 7 cells (both GFP-positive and GFP-negative).…”

Section: Differential Changes In Gene Expressionmentioning

confidence: 99%

Essential Alterations of Heparan Sulfate During the Differentiation of Embryonic Stem Cells to Sox1-Enhanced Green Fluorescent Protein-Expressing Neural Progenitor Cells

et al. 2007

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Embryonic stem (ES) cells can be cultured in conditions thateither maintain pluripotency or allow differentiation to the three embryonic germ layers. Heparan sulfate (HS), a highly polymorphic glycosaminoglycan, is a critical cell surface coreceptor in embryogenesis, and in this paper we describe its structural transition from an unusually low-sulfated variant in ES cells to a more highly sulfated form in fluorescence-activated cell sorting-purified neural progenitor cells. The characteristic domain structure of HS was retained during this transformation. However, qualitative variations in surface sulfation patterns between ES and differentiated cells were revealed using HS epitope-specific antibodies and the HS-binding growth factor fibroblast growth factor 2 (FGF-2). Expression profiles of the HS modification enzymes indicated that both "early" (N-sulfotransferases) and "late" (6O-and 3O-sulfotransferases) sulfotransferases contributed to the alterations in sulfation patterning. An HS-null ES line was used to demonstrate the necessity for HS in neural differentiation. HS is a coreceptor for many of the protein effectors implicated in pluripotency and differentiation (e.g., members of the FGF family, bone morphogenic proteins, and fibronectin). We suggest that the stage-specific activities of these proteins are finely regulated by dynamic changes in sulfation motifs in HS chains.

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Mouse Testican-2

Cited by 56 publications

References 26 publications

DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers

DNA Methylation Profiling in Pheochromocytoma and Paraganglioma Reveals Diagnostic and Prognostic Markers

A Genomic Comparison of in vivo and in vitro Brain Microvascular Endothelial Cells

Essential Alterations of Heparan Sulfate During the Differentiation of Embryonic Stem Cells to Sox1-Enhanced Green Fluorescent Protein-Expressing Neural Progenitor Cells

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