Detection of Autocrine Motility Factor in Urine as a Marker of Bladder Cancer

Abstract

Cell locomotion is an essential requirement for invasion and metastasis of malignant cells. We have previously described the characterization of a 50-kilodalton autocrine motility factor (AMF), a cytokine that stimulates motility in human tumor cells. In this study, we investigated the elaboration of this factor in vivo by human bladder carcinoma and in vitro by a cultured transitional cell carcinoma (TCC) of the bladder cell line T24P. Urine samples from patients with bladder cancer were assayed for their capacity to stimulate migration of tumor cells. Comparing all TCC cases (22 patients) with all nonmalignant diagnoses (27 patients), we found a statistically significant (P less than .001) difference in the motility values. Invasive TCC cases (15 patients) were significantly (P less than .002) higher in regard to motility values compared with noninvasive TCC cases (8 patients), including one case of carcinoma in situ. In follow-up screening studies evaluating TCC recurrence, the recurrent tumors (9 patients) were higher (P less than .001) in regard to motility values than the tumor-free cases (11 patients). Furthermore, T24P cells showed a dose-dependent motile response to their own serum-free conditioned medium as well as to the AMF present in the urine of TCC patients. This finding is consistent with the source of AMF in the urine of these patients being the cancer itself. An enzyme-linked immunosorbent assay (ELISA) for AMF was also developed. Values determined by ELISA correlated well with the motility values measured separately. These data support the potential usefulness of AMF as a urine marker for bladder TCC.