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

• Published in: Virchows Archiv : an international journal of pathology 2012-10, Vol.461 (4), p.475-481
• Main Authors: Waaijer, Cathelijn J F, de Andrea, Carlos E, Hamilton, Andrew, van Oosterwijk, Jolieke G, Stringer, Sally E, Bovée, Judith V M G
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - metabolism; Biopsy; Bone; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Cell Line, Tumor; Cells, Cultured; Chondrocytes - metabolism; Chondrocytes - pathology; Chondrosarcoma - metabolism; Chondrosarcoma - pathology; Disease Progression; Fibroblast Growth Factors - metabolism; Follow-Up Studies; Growth factors; Humans; In Vitro Techniques; Liquid chromatography; Medicine; Medicine & Public Health; Microarray Analysis; Original Article; Pathology; Signal Transduction - physiology; Sulfates; Sulfotransferases - metabolism; Wnt Proteins - metabolism
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-012-1300-5

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 6 O position plays a pivotal role. 6 O -Sulphation occurs through three HS 6 O -sulphotransferases (HS6ST1-3) and is fine-tuned by two endosulphatases (SULF1-2) that remove 6 O -sulphate groups. We have investigated whether the expression of HS6STs and SULFs changes during chondrosarcoma progression and have determined 6 O -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 6 O -sulphation is increased during progression. This was confirmed in one grade III chondrosarcoma cell line, which showed a dramatically increased 6 O -sulphation compared to an articular chondrocyte cell line by HPLC; another cell line showed an increased expression of one 6 O -sulphated HS disaccharide. In conclusion, our results show increased HS6ST1 and HS6ST2 expression during chondrosarcoma progression and increased HS 6 O -sulphation in vitro. As 6 O -sulphation plays an important role in signal transduction, altered HS6ST expression might be associated with changes in signal transduction pathways in chondrosarcoma progression.