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Primary ovarian carcinomas and abdominal metastasis contain 4,6-disulfated chondroitin sulfate rich regions, which provide adhesive properties to tumour cells.

Vallen MJ, Schmidt S, Oosterhof A, Bulten J, Massuger LF, van Kuppevelt TH - PLoS ONE (2014)

Bottom Line: Increased expression of CSE reduced cell migration.Addition of free CSE had similar effects.The data presented here indicate that CSE is associated with metastatic lesions and that it provides tumours with adhesive properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.

ABSTRACT
High mortality in ovarian cancer patients is primarily caused through rapid metastasis of the tumour, but the underlying mechanisms are poorly understood. Glycosaminoglycans, are abundantly present in tumours and chondroitin sulfate-E (CSE), a highly 4,6-sulfated glycosaminoglycan, has been indicated to play a role in carcinogenesis. In this study we investigated the presence of CSE in ovarian cancer metastasis and studied its role in tumour cell adhesiveness and migration. CSE was studied immunohistochemically in primary ovarian carcinomas and abdominal metastases using the single chain antibody GD3G7. The role of CSE was studied in 2D (scratch assays) and 3D (collagen matrices, spheroids) systems using SKOV3 cells applying 1: overexpression of CSE by stable transfection with DNA encoding GalNAc4S-6 sulfotransferase, 2: enzymatic removal of CS, and 3: addition of CSE. In ovarian cancer tissue, CSE expression was predominantly seen in the stromal compartment of both primary ovarian carcinomas and metastases, with a comparable degree of intensity and extent. Overexpression of CSE disaccharide units by tumour cells increased their adhesive properties which was especially seen in tumour spheroid formation. Increased expression of CSE reduced cell migration. Addition of free CSE had similar effects. The data presented here indicate that CSE is associated with metastatic lesions and that it provides tumours with adhesive properties. CSE rich motifs are put forward as a potential target for ovarian cancer therapy.

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Increase of staining for CSE in SKOV3 cells transfected with GalNAc4S-6ST (antibody GD3G7).SKOV3 wildtype (A) and transfection control (empty vector) SKOV3(-) cells (C5 (B) and C6 (C)) showed weak (peri)cellular expression of CSE, whereas SKOV3 cells transfected with DNA encoding GalNAc4S-6ST (F5(D), F7(E), F9(F)) showed strong expression for CSE expression, especially in more dense regions. Bar: 100 µm.
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pone-0111806-g003: Increase of staining for CSE in SKOV3 cells transfected with GalNAc4S-6ST (antibody GD3G7).SKOV3 wildtype (A) and transfection control (empty vector) SKOV3(-) cells (C5 (B) and C6 (C)) showed weak (peri)cellular expression of CSE, whereas SKOV3 cells transfected with DNA encoding GalNAc4S-6ST (F5(D), F7(E), F9(F)) showed strong expression for CSE expression, especially in more dense regions. Bar: 100 µm.

Mentions: Using confluent cells, the wildtype SKOV3 cells as well the cells containing the empty vector showed weak to moderate (peri)cellular staining with antibody GD3G7 (fig. 3A–C), whereas cells transfected with the DNA encoding GalNAc4S-6ST showed more abundant staining, including areas of very strong staining intensity (fig 3D–F).


Primary ovarian carcinomas and abdominal metastasis contain 4,6-disulfated chondroitin sulfate rich regions, which provide adhesive properties to tumour cells.

Vallen MJ, Schmidt S, Oosterhof A, Bulten J, Massuger LF, van Kuppevelt TH - PLoS ONE (2014)

Increase of staining for CSE in SKOV3 cells transfected with GalNAc4S-6ST (antibody GD3G7).SKOV3 wildtype (A) and transfection control (empty vector) SKOV3(-) cells (C5 (B) and C6 (C)) showed weak (peri)cellular expression of CSE, whereas SKOV3 cells transfected with DNA encoding GalNAc4S-6ST (F5(D), F7(E), F9(F)) showed strong expression for CSE expression, especially in more dense regions. Bar: 100 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221137&req=5

pone-0111806-g003: Increase of staining for CSE in SKOV3 cells transfected with GalNAc4S-6ST (antibody GD3G7).SKOV3 wildtype (A) and transfection control (empty vector) SKOV3(-) cells (C5 (B) and C6 (C)) showed weak (peri)cellular expression of CSE, whereas SKOV3 cells transfected with DNA encoding GalNAc4S-6ST (F5(D), F7(E), F9(F)) showed strong expression for CSE expression, especially in more dense regions. Bar: 100 µm.
Mentions: Using confluent cells, the wildtype SKOV3 cells as well the cells containing the empty vector showed weak to moderate (peri)cellular staining with antibody GD3G7 (fig. 3A–C), whereas cells transfected with the DNA encoding GalNAc4S-6ST showed more abundant staining, including areas of very strong staining intensity (fig 3D–F).

Bottom Line: Increased expression of CSE reduced cell migration.Addition of free CSE had similar effects.The data presented here indicate that CSE is associated with metastatic lesions and that it provides tumours with adhesive properties.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Obstetrics and Gynaecology, Radboud University Medical Center, Nijmegen, The Netherlands.

ABSTRACT
High mortality in ovarian cancer patients is primarily caused through rapid metastasis of the tumour, but the underlying mechanisms are poorly understood. Glycosaminoglycans, are abundantly present in tumours and chondroitin sulfate-E (CSE), a highly 4,6-sulfated glycosaminoglycan, has been indicated to play a role in carcinogenesis. In this study we investigated the presence of CSE in ovarian cancer metastasis and studied its role in tumour cell adhesiveness and migration. CSE was studied immunohistochemically in primary ovarian carcinomas and abdominal metastases using the single chain antibody GD3G7. The role of CSE was studied in 2D (scratch assays) and 3D (collagen matrices, spheroids) systems using SKOV3 cells applying 1: overexpression of CSE by stable transfection with DNA encoding GalNAc4S-6 sulfotransferase, 2: enzymatic removal of CS, and 3: addition of CSE. In ovarian cancer tissue, CSE expression was predominantly seen in the stromal compartment of both primary ovarian carcinomas and metastases, with a comparable degree of intensity and extent. Overexpression of CSE disaccharide units by tumour cells increased their adhesive properties which was especially seen in tumour spheroid formation. Increased expression of CSE reduced cell migration. Addition of free CSE had similar effects. The data presented here indicate that CSE is associated with metastatic lesions and that it provides tumours with adhesive properties. CSE rich motifs are put forward as a potential target for ovarian cancer therapy.

Show MeSH
Related in: MedlinePlus