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

Universidad Pontificia de 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 65

Subject Categories

Clinical Laboratory Medicine

Urology and Nephrology

Cancer and Oncology

DOI

10.1038/s41420-020-00304-z

More information

Latest update

8/26/2020