Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

Gill, Roop; Mehra, Vedika; Milford, Emma; Dhoot, Gurtej K.

doi:10.1007/s00418-016-1454-3

Cited by 12 publications

(10 citation statements)

References 35 publications

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“…93 Dhoot et al demonstrated that SULF2 can be expressed as an alternatively spliced catalytically inactive variant and found that various tumors express this at high levels. [94][95][96] Mechanistically, the inactive variant titrates out the active variant and results in an increase in 6-O sulfation and receptor tyrosine kinase activation. It would thus also be important to check which splice variants of SULF2 are expressed in macrophages and other immune cell types during chronic inflammation.…”

Section: Sulfatasesmentioning

confidence: 99%

Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Swart

Troeberg

2018

J Histochem Cytochem.

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Heparan sulfate (HS) proteoglycans on immune cells have the ability to bind to and regulate the bioactivity more than 400 bioactive protein ligands, including many chemokines, cytokines, and growth factors. This makes them important regulators of the phenotype and behavior of immune cells. Here we review how HS biosynthesis in macrophages is regulated during polarization and in chronic inflammatory diseases such as rheumatoid arthritis, atherosclerosis, asthma, chronic obstructive pulmonary disease and obesity, by analyzing published micro-array data and mechanistic studies in this area. We describe that macrophage expression of many HS biosynthesis and core proteins is strongly regulated by macrophage polarization, and that these expression patterns are recapitulated in chronic inflammation. Such changes in HS biosynthetic enzyme expression are likely to have a significant impact on the phenotype of macrophages in chronic inflammatory diseases by altering their interactions with chemokines, cytokines, and growth factors. (J Histochem Cytochem 67:9-27, 2019)

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Section: Sulfatasesmentioning

confidence: 99%

Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Swart

Troeberg

2018

J Histochem Cytochem.

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“…Tissue sections for morphological observations were stained with a standard haematoxylin and eosin stain. Double immunofluorescent procedure as described previously 14 was used to evaluate the cellular phenotypes of normal and 15 HCC tissues. Following commercial antibodies were used for this analysis: Wnt2 (Prestige)-1/150, active caspase-3 (R&D)-1/100, ptc1 (Millipore)-1/300, p-Smad1,5,8 (Cell signalling)-1/300, HIF1α (Novus)-1/40, EpoR (Abcam)-1/250, Glycophorin A (Abcam)-1/10, Cytokeratin 18 (Abcam)-1/300, smooth muscle α-actin (IA4)-1/400, vWF 15 (Dako)-1/200, rabbit anti CD146 (Sigma)-1/200, mouse anti NANOG (Abcam)-1/100 and rabbit anti OCT4 (Novus biologicals)-1/100.…”

Section: Methodsmentioning

confidence: 99%

“…With the exception of Glycophorin A antibody that itself is linked to 488 fluorochrome, the binding of all other antibodies was detected by secondary antibodies linked to 488 (green) fluorochrome or 594 (red) fluorochrome as previously described. 14 Immunoperoxidase staining was used to detect the expression pattern of active-β-catenin (Millipore) antibody using 1/100 dilution as previously described. 16…”

Section: Methodsmentioning

confidence: 99%

Dysregulated cancer cell transdifferentiation into erythrocytes is an additional metabolic stress in hepatocellular carcinoma

Hughes

Dhoot

2018

Tumour Biol.

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A number of human and canine hepatocellular carcinoma tissues showed clear signs of hypoxia indicated by HIF1a-activation and the presence of large clusters of cells resembling erythrocytes at different stages of nuclear elimination without any defined endothelial cell lining or blood vessel walls. Differentiated erythrocytic identity of such cells in hepatocellular carcinoma tissues was apparent from their non-nucleated and evolving basophilic to eosinophilic staining characteristics. In addition to the fully differentiated non-nucleated mesenchymal cell clusters, the onset of erythroblastic transdifferentiation was apparent from the activation of Glycophorin A, a marker of erythrocytic progenitors, in some epithelial cancer cells. Activation of canonical Wnt signalling in such tumours was apparent from the expression of Wnt2 ligand and active b-catenin translocation into the nucleus indicating Wnt signalling to be one of the key signalling pathways participating in such cell transdifferentiation. Sonic hedgehog and bone morphogenetic protein signalling along with Sulf1/Sulf2 activation was also observed in such hepatocellular carcinoma tissue samples. The presence of stem cell markers and the cell signalling pathways associated with erythropoiesis, and the detection of messenger RNAs for both a and b haemoglobins, support the assumption that hepatocellular carcinoma cells have the potential to undergo cell fate change despite this process being dysregulated as indicated by the lack of simultaneous generation of endothelial cell lining. Lack of blood vessel walls or endothelial cell lining around erythrocytic clusters was confirmed by non-detection of multiple blood vessel markers such as vWF, CD146 and smooth muscle a-actin that were clearly apparent in normal and unaffected adjacent regions of hepatocellular carcinoma livers. In addition to the activation of Glycophorin A, transdifferentiation of some hepatocellular carcinoma hepatocytes into other cell fates was further confirmed by the activation of some stem cell markers, for example, NANOG and OCT4 transcription factors, not only by reverse transcription polymerase chain reaction but also by their restricted expression in such cells at protein level.

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“…However, ligands are often sequestered in the extracellular matrix (ECM) which need to be liberated for them to activate their receptor. We have previously shown that de-sulfation of the ECM mediated by SULF1/SULF2 enzymes regulates signalling pathways during development, regeneration and disease [1,[9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Dysregulated cell signalling and reduced satellite cell potential in ageing muscle

Patel

Simbi

Ritvos

et al. 2019

Experimental Cell Research

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Short SULF1/SULF2 splice variants predominate in mammary tumours with a potential to facilitate receptor tyrosine kinase-mediated cell signalling

Cited by 12 publications

References 35 publications

Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Effect of Polarization and Chronic Inflammation on Macrophage Expression of Heparan Sulfate Proteoglycans and Biosynthesis Enzymes

Dysregulated cancer cell transdifferentiation into erythrocytes is an additional metabolic stress in hepatocellular carcinoma

Dysregulated cell signalling and reduced satellite cell potential in ageing muscle

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