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| Status |
Public on Aug 23, 2013 |
| Title |
Gene expression of SKOV3 cells after no treatment or treatment with 50 microM peracetylated GlcNAc or peracetylated 4-deoxy-GlcNAc for three days |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Heparan sulfate (HS), a long linear polysaccharide, is implicated in various steps of tumorigenesis, including angiogenesis. We successfully interfered with HS biosynthesis using a peracetylated 4-deoxy analog of the HS constituent GlcNAc and studied the compound’s metabolic fate and its effect on angiogenesis. The 4-deoxy analog was activated intracellularly into UDP-4-deoxy-GlcNAc and HS expression was inhibited up to ~96% (IC50 = 16 µM). HS chain size was reduced, without detectable incorporation of the 4-deoxy analog, likely due to reduced levels of UDP-GlcNAc and/or inhibition of glycosyltransferase activity. Comprehensive gene expression analysis revealed reduced expression of genes regulated by HS binding growth factors as FGF-2 and VEGF. Cellular binding and signaling of these angiogenic factors was inhibited. Micro-injection in zebrafish embryos strongly reduced HS biosynthesis, and angiogenesis was inhibited in both zebrafish and chicken model systems. All these data identify 4-deoxy-GlcNAc as a potent inhibitor of HS synthesis which hampers pro-angiogenic signaling and neo-vessel formation.
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| Overall design |
9 samples were analyzed: 3 biological replicates from untreated SKOV3 cells, 3 biological replicates from SKOV3 cells treated with peracetylated GlcNAc, 3 biological replicates from SKOV3 cells treated with peracetylated 4-deoxy-GlcNAc
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| Contributor(s) |
van Wijk XM, van de Westerlo EM, Verwiel ET, van Kuppevelt TH |
| Citation(s) |
23972127 |
| Submission date |
Jun 25, 2013 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Xander M van Wijk |
| E-mail(s) |
xvanwijk@ucsd.edu
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| Organization name |
Radboud University Nijmegen Medical Centre
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| Department |
Biochemistry
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| Street address |
Geert Grooteplein 26-28
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| City |
Nijmegen |
| ZIP/Postal code |
6525 GA |
| Country |
Netherlands |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA209515 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48284_RAW.tar |
214.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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