Highly sulfated chondroitin sulfates, a novel class of prognostic biomarkers in ovarian cancer tissue

Vallen, Myrtille J.E.; Massuger, Leon F.A.G.; Dam, Gerdy B. ten; Bulten, Johan; Kuppevelt, Toin H. Van

doi:10.1016/j.ygyno.2012.06.022

Cited by 49 publications

(29 citation statements)

References 29 publications

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“…The proportion of E units in CS-DS chains is elevated in ovarian and pancreatic cancers, resulting in alterations in neoplastic growth and cell motility through control of the signaling of vascular endothelial growth factor and cleavage of CD44, respectively [24,25]. The stronger expression of disulfated E disaccharide units has also been observed on CS-DS chains at the surface of metastatic Lewis lung carcinoma (LLC) cells [26].…”

Section: Cs-e Interactions With Rage Involved In Tumor Metastasismentioning

confidence: 99%

Molecular interactions between chondroitin–dermatan sulfate and growth factors/receptors/matrix proteins

Mizumoto

Yamada

Sugahara

2015

Current Opinion in Structural Biology

185

121

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Section: Cs-e Interactions With Rage Involved In Tumor Metastasismentioning

confidence: 99%

Molecular interactions between chondroitin–dermatan sulfate and growth factors/receptors/matrix proteins

Mizumoto

Yamada

Sugahara

2015

Current Opinion in Structural Biology

185

121

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“…Using an antibody recognizing a motif that is rich in CSE units (GD3G7), we recently showed strong upregulation of CSE in primary ovarian carcinomas which correlated with poor prognostic parameters such as high grade, and advanced FIGO stage [19]. Interference with CSE, either by blockage using GD3G7 or by enzymatic degradation of CS chains, strongly inhibited metastatic growth in a mouse Lewis lung carcinoma model [22].…”

Section: Introductionmentioning

confidence: 99%

Primary Ovarian Carcinomas and Abdominal Metastasis Contain 4,6-Disulfated Chondroitin Sulfate Rich Regions, Which Provide Adhesive Properties to Tumour Cells

Vallen

Schmidt²,

Oosterhof

et al. 2014

PLoS ONE

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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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“…In addition, the sulfation pattern alters during dedifferentiation, showing increased rates of non-and disulfated disaccharides and decreased levels of monosulfated disaccharides. Concerning the different ovarian cancer subtypes, serous ovarian carcinomas show an increased amount of CS-E compared to mucinous ovarian carcinomas [7]. In conclusion, CS might represent an intermediate molecule in specific molecular pathways of ovarian cancer development.…”

Section: Ovarian Cancer Oncogenesismentioning

confidence: 87%

“…An increase of CS and its different subfamilies has been noted in various types of cancer, including ovarian cancer (Table 1). Moreover, elevated levels of unique CS epitopes in ovarian cancer tissue and patient sera are associated with adverse prognostic factors and poor patient outcome [6,7]. The functional significance of CS accumulation is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: ‘When sweet turns sour’

Vallen

Steen

Tilborg

et al. 2014

Gynecologic Oncology

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Highly sulfated chondroitin sulfates, a novel class of prognostic biomarkers in ovarian cancer tissue

Cited by 49 publications

References 29 publications

Molecular interactions between chondroitin–dermatan sulfate and growth factors/receptors/matrix proteins

Molecular interactions between chondroitin–dermatan sulfate and growth factors/receptors/matrix proteins

Primary Ovarian Carcinomas and Abdominal Metastasis Contain 4,6-Disulfated Chondroitin Sulfate Rich Regions, Which Provide Adhesive Properties to Tumour Cells

Sulfated sugars in the extracellular matrix orchestrate ovarian cancer development: ‘When sweet turns sour’

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