Changes in composition and sulfation patterns of glycoaminoglycans in renal cell carcinoma

Uçaktürk, Ebru; Akman, Orkun; Sun, Xiaojun; Baydar, Dilek Ertoy; Dolgun, Anıl; Zhang, Fuming; Linhardt, Robert J.

doi:10.1007/s10719-015-9643-1

Cited by 24 publications

(22 citation statements)

References 58 publications

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“…For example, VEGF levels may be derived from damaged platelets, while amyloid A is a renowned marker of trauma and various inflammations. Conversely, we and other groups previously provided evidence that the increase of GAG levels in ccRCC patients is likely a product of the tumor itself (30), possibly due to the upregulation of the GAG biosynthetic pathway (14). In addition, the here-reported HRs for the urine score were not only predictors of poor survival in a continuous an independent fashion, but also of much higher magnitude compared to the above mentioned biomarkers (multivariate HR = 5.38 for PFS and 16.43 for OS).…”

Section: Resultsmentioning

confidence: 63%

Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma

et al. 2016

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BackgroundThe prognosis of metastatic clear cell renal cell carcinoma (ccRCC) vastly improved since the introduction of antiangiogenic-targeted therapy. However, it is still unclear which biological processes underlie ccRCC aggressiveness and affect prognosis. Here, we checked whether a recently discovered systems biomarker based on plasmatic or urinary measurements of glycosaminoglycans (GAGs) aggregated into diagnostic scores correlated with ccRCC prognosis.MethodsThirty-one patients with a diagnosis of ccRCC (23 metastatic) were prospectively enrolled, and their urine and plasma biomarker scores were correlated to progression-free survival (PFS) and overall survival (OS) as either a dichotomous (“Low” vs. “High”) or a continuous variable in a multivariate survival analysis.ResultsThe survival difference between “High”- vs. “Low”-scored patients was significant in the case of urine scores (2-year PFS rate = 53.3 vs. 100%, p = 3 × 10−4 and 2-year OS rate = 73.3 vs. 100%, p = 0.0078) and in the case of OS for plasma scores (2-year PFS rate = 60 vs. 84%, p = 0.0591 and 2-year OS rate = 66.7 vs. 90%, p = 0.0206). In multivariate analysis, the urine biomarker score as a continuous variable was an independent predictor of PFS [hazard ratio (HR): 4.62, 95% CI: 1.66–12.83, p = 0.003] and OS (HR: 10.13, 95% CI: 1.80–57.04, p = 0.009).ConclusionThis is the first report on an association between plasma or urine GAG scores and the prognosis of ccRCC patients. Prospective trials validating the prognostic and predictive role of this novel systems biomarker are warranted.

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Section: Resultsmentioning

confidence: 63%

Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma

et al. 2016

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“…These disturbances are manifested as a changed sulfation pattern of CS/DS that has common features regardless of the tumor type. First and foremost, a substantial increase in the content of the 6‐ O ‐sulfated and/or unsulfated disaccharides that is observed in a huge majority of cancers is concomitant with a reduction in the 4‐ O ‐sulfation level (Table ). The observed loss of 4‐ O ‐sulfated GalNAc may be one reason for the disappearance of the IdoA residues despite the tumor‐associated upregulation of glucuronic epimerase, which has been found to be characteristic in human cancers such as squamous carcinoma or glioblastoma .…”

Section: The Metabolism Of Cs/ds Is Strongly Altered In the Tumor Stromamentioning

confidence: 99%

“…Unfortunately, only a few studies have focused on this aspect of CS/DS metabolism in the tumor niche . These investigations have reported that the contribution of various disulfated disaccharides to the composition of CS/DS is cancer type‐ and cancer grade‐dependent (Table ). The accumulation of disulfated disaccharides in the CS/DS that exist in the tumor microenvironment can substantially modulate the progression and metastasis of a tumor due to the increased binding potential of these disaccharides .…”

Section: The Metabolism Of Cs/ds Is Strongly Altered In the Tumor Stromamentioning

confidence: 99%

“…The tumor-associated remodeling of the CS/DS sulfation pattern can also affect the disulfated disaccharide content. Unfortunately, only a few studies have focused on this aspect of CS/DS metabolism in the tumor niche [72,74,75,78,81,85,86]. These investigations have reported that the contribution of various disulfated disaccharides to the composition of CS/DS is cancer type-and cancer grade-dependent [72,74,75,78,81,85,86] (Table 1).…”

Section: Cs and Ds Are Both Structurally Heterogeneousmentioning

confidence: 99%

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The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

et al. 2019

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The remarkable structural heterogeneity of chondroitin sulfate (CS) and dermatan sulfate (DS) generates biological information that can be unique to each of these glycosaminoglycans (GAGs), and changes in their composition are translated into alterations in the binding profiles of these molecules. CS/DS can bind to various cytokines and growth factors, cell surface receptors, adhesion molecules, enzymes and fibrillar glycoproteins of the extracellular matrix, thereby influencing both cell behavior and the biomechanical and biochemical properties of the matrix. In this review, we summarize the current knowledge concerning CS/DS metabolism in the human cancer stroma. The remodeling of the GAG profile in the tumor niche is manifested as a substantial increase in the CS content and a gradual decrease in the proportion between DS and CS. Furthermore, the composition of CS and DS is also affected, which results in a substantial increase in the 6‐O‐sulfated and/or unsulfated disaccharide content, which is concomitant with a decrease in the 4‐O‐sulfation level. Here, we discuss the possible impact of alterations in the CS/DS sulfation pattern on the binding capacity and specificity of these GAGs. Moreover, we propose potential consequences of the stromal accumulation of chondroitin‐6‐sulfate for the progression and metastasis of cancer.

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“…This is motivated by the implication of ECM GAG and their PG in a wide variety of biological processes, including embryonic development [11,12], infection [13], inflammation [6,14], wound healing [8] and cancer [14][15][16]. Variation in ECM GAG content and composition is also tissue-specific, age-dependent [17,18] and known to be associated with certain pathologies [19,20]. (2) Chondroitin Sulfate and Dermatan Sulfate also share the same amino sugar unit (GalNac) but their uronic unit is β-d-GlcA and α-l-IdoA, respectively.…”

Section: Introductionmentioning

confidence: 99%

Glycosaminoglycan-Inspired Biomaterials for the Development of Bioactive Hydrogel Networks

et al. 2020

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Glycosaminoglycans (GAG) are long, linear polysaccharides that display a wide range of relevant biological roles. Particularly, in the extracellular matrix (ECM) GAG specifically interact with other biological molecules, such as growth factors, protecting them from proteolysis or inhibiting factors. Additionally, ECM GAG are partially responsible for the mechanical stability of tissues due to their capacity to retain high amounts of water, enabling hydration of the ECM and rendering it resistant to compressive forces. In this review, the use of GAG for developing hydrogel networks with improved biological activity and/or mechanical properties is discussed. Greater focus is given to strategies involving the production of hydrogels that are composed of GAG alone or in combination with other materials. Additionally, approaches used to introduce GAG-inspired features in biomaterials of different sources will also be presented.

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Changes in composition and sulfation patterns of glycoaminoglycans in renal cell carcinoma

Cited by 24 publications

References 58 publications

Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma

Prognostic Value of Plasma and Urine Glycosaminoglycan Scores in Clear Cell Renal Cell Carcinoma

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

Glycosaminoglycan-Inspired Biomaterials for the Development of Bioactive Hydrogel Networks

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