A simple method for detecting oncofetal chondroitin sulfate glycosaminoglycans in bladder cancer urine
Journal article, 2020
Proteoglycans in bladder tumors are modified with a distinct oncofetal chondroitin sulfate (ofCS) glycosaminoglycan that is normally restricted to placental trophoblast cells. 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. In bladder cancer, proteoglycans are constantly shed into the urine, and therefore have the potential to be used for detection of disease. 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. 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. Patients with high-grade bladder tumors displayed a marked increase in urinary ofCSPGs as compared to healthy individuals. Urine ofCSPGs decreased significantly after complete tumor resection compared to matched urine collected preoperatively from patients with bladder cancer. Moreover, ofCSPGs in urine correlated with tumor size of bladder cancer patients. 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.
Author
Thomas Mandel Clausen
Vancouver Prostate Centre
University of British Columbia (UBC)
University of Copenhagen
Gunjan Kumar
Vancouver Prostate Centre
University of British Columbia (UBC)
Emilie K. Ibsen
University of Copenhagen
Maj S. Ørum-Madsen
Vancouver Prostate Centre
University of British Columbia (UBC)
Antonio Hurtado-Coll
University of British Columbia (UBC)
Vancouver Prostate Centre
Tobias Gustavsson
University of Copenhagen
Mette Agerbæk
University of Copenhagen
VarCT Diagnostics ApS
Francesco Gatto
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Tilman Todenhöfer
University of Tübingen
Clinical Trial Unit
U. Basso
IRCCS Istituto Oncologico Veneto IOV
Margaret A. Knowles
St James's University Hospital
Marta Sanchez-Carbayo
Pontifical University of Salamanca
Ali Salanti
University of Copenhagen
Peter C. Black
Vancouver Prostate Centre
University of British Columbia (UBC)
Mads Daugaard
University of British Columbia (UBC)
Vancouver Prostate Centre
Cell Death Discovery
20587716 (eISSN)
Vol. 6 1 65Subject Categories
Clinical Laboratory Medicine
Urology and Nephrology
Cancer and Oncology
DOI
10.1038/s41420-020-00304-z