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Virchows Archiv
Published in: Virchows Archiv 4/2012

01-10-2012 | Original Article

Cartilage tumour progression is characterized by an increased expression of heparan sulphate 6O-sulphation-modifying enzymes

Authors: Cathelijn J F Waaijer, Carlos E de Andrea, Andrew Hamilton, Jolieke G van Oosterwijk, Sally E Stringer, Judith V M G Bovée

Published in: Virchows Archiv | Issue 4/2012

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Abstract

Chondrosarcomas are malignant cartilage-forming tumours that can arise centrally (in the medulla) or peripherally (at the surface) of the bone. They are classified into three histological grades which correspond to the clinical severity. Previous studies by our group have shown altered signal transduction of the fibroblast growth factor and Wnt signalling pathways during peripheral chondrosarcoma progression. Heparan sulphate (HS) is a glycosaminoglycan that facilitates receptor binding of multiple growth factors, in which the sulphation of 6O position plays a pivotal role. 6O-Sulphation occurs through three HS 6O-sulphotransferases (HS6ST1-3) and is fine-tuned by two endosulphatases (SULF1-2) that remove 6O-sulphate groups. We have investigated whether the expression of HS6STs and SULFs changes during chondrosarcoma progression and have determined 6O-sulphation levels in two chondrosarcoma cell lines. Immunohistochemistry on tissue microarrays of chondrosarcomas showed that HS6ST3 and SULF1 were highly expressed in most chondrosarcomas, whereas SULF2 expression was absent in most cases. HS6ST1 and HS6ST2 expression are significantly increased during chondrosarcoma progression, which suggest that 6O-sulphation is increased during progression. This was confirmed in one grade III chondrosarcoma cell line, which showed a dramatically increased 6O-sulphation compared to an articular chondrocyte cell line by HPLC; another cell line showed an increased expression of one 6O-sulphated HS disaccharide. In conclusion, our results show increased HS6ST1 and HS6ST2 expression during chondrosarcoma progression and increased HS 6O-sulphation in vitro. As 6O-sulphation plays an important role in signal transduction, altered HS6ST expression might be associated with changes in signal transduction pathways in chondrosarcoma progression.
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Metadata
Title
Cartilage tumour progression is characterized by an increased expression of heparan sulphate 6O-sulphation-modifying enzymes
Authors
Cathelijn J F Waaijer
Carlos E de Andrea
Andrew Hamilton
Jolieke G van Oosterwijk
Sally E Stringer
Judith V M G Bovée
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Virchows Archiv / Issue 4/2012
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-012-1300-5

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