While the basic structure is simple, an immense structural heterogeneity is achieved through modifications of the carbohydrate backbone, such as sulfation of component hydroxyl groups. CS chains are comprised of linear polysaccharides made up of repeated N-acetyl-D-galactosamine (GalNAc) and Glucuronic Acid (GlcA) disaccharide units and can vary greatly in length. While several urine biomarkers have been identified over the years, novel biomarkers with high sensitivity and specificity are in demand 5.Ĭhondroitin Sulfate (CS) is a glycosaminoglycan (GAG) linked to specific proteoglycans (CSPGs) present in the cell membranes, or secreted into the extracellular matrix and bodily fluids 6. Urinary biomarkers in bladder cancer have been researched for decades with the aim of noninvasive detection of disease and to monitor high-risk patients with nonmuscle invasive bladder cancer (NMIBC) 3, 4, 5. These findings demonstrate that rVAR2 can be utilized in a simple biochemical assay to detect cancer-specific ofCS-modifications in the urine of bladder cancer patients, which may be further developed as a noninvasive approach to detect and monitor the disease.īladder cancer is the fifth most common cancer in the world and one of the most expensive cancers to treat on a per-patient basis due to the need for constant surveillance and multiple therapeutic interventions 1, 2. Moreover, ofCSPGs in urine correlated with tumor size of bladder cancer patients. Urine ofCSPGs decreased significantly after complete tumor resection compared to matched urine collected preoperatively from patients with bladder cancer. Patients with high-grade bladder tumors displayed a marked increase in urinary ofCSPGs as compared to healthy individuals. We show that ofCSPGs in bladder cancer urine can be immobilized on cationic nitrocellulose membranes and subsequently probed for ofCS content by rVAR2 protein in a custom-made dot-blot assay. In this study we investigated whether recombinant VAR2CSA (rVAR2) protein could be used to detect ofCS-modified proteoglycans (ofCSPGs) in the urine of bladder cancer patients as an indication of disease presence. In bladder cancer, proteoglycans are constantly shed into the urine, and therefore have the potential to be used for detection of disease. This ofCS-modification can be detected in bladder tumors by the malarial VAR2CSA protein, which in malaria pathogenesis mediates adherence of parasite-infected erythrocytes within the placenta. Proteoglycans in bladder tumors are modified with a distinct oncofetal chondroitin sulfate (ofCS) glycosaminoglycan that is normally restricted to placental trophoblast cells.
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