USE OF PROSTATE SPECIFIC ANTIGEN TO MEASURE BLADDER TUMOR GROWTH IN A MOUSE ORTHOTOPIC MODEL

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Animal orthotopic tumor models are commonly used in bladder cancer studies. However, to our knowledge there is currently no accurate method to quantify tumor growth inside the bladder in living animals. We used prostate specific antigen (PSA) as a marker to cope with this limitation. Infectious but replication incompetent retroviral particles carrying PSA coding sequence were constructed and infected into MB49 cells, a mouse bladder transitional cell carcinoma line of C57BL/6 origin. Syngeneic mice were intravesically implanted with the novel MB49-PSA transfectants. Tumor burden was evaluated by enzyme-linked immunosorbent assay measurement for PSA in urine and bladder tissues. The MB49-PSA line actively secreted PSA in culture as well as in urine (18 to 2,062 pg/ml) depending on tumor mass. Immunofluorescence staining confirmed PSA expression in MB49-PSA derived orthotopic tumors. Urinary PSA production paralleled tumor growth and was detectable prior to the development of a palpable tumor. Although urinary PSA did not tightly correlate with tumor mass, all bladders (total of 16 tested) weighing 34 mg or greater (18 to 21 mg for age and sex matched normal bladders) showed 18 pg/ml or greater urinary PSA. In contrast, bladder tissue PSA correlated more with tumor mass in general and it was measurable even before the detection of urinary PSA. This MB49-PSA orthotopic tumor model also demonstrated its usefulness for evaluating the antibladder cancer agents gemcitabine and mitomycin. This novel MB49-PSA line may serve as a useful tool for bladder cancer study because its growth inside the bladder can be noninvasively measured in living animals even during early stages of tumor growth.