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.

Autocrine Motility Factor in Pulmonary Adenocarcinomas: Results of an Immunohistochemical Study

“…Serum PHI activities were shown to serve as a tumor marker for monitoring patients with malignant tumors [12,13], and elevation in the PHI activity was shown to be closely correlated with the development of metastases [14]. It was reported that the presence of AMF in the urine is a marker of transitional cell carcinoma of the bladder [15]. AMF stimulates cell motility via binding to its receptor (AMF-R, gp-78).…”

“…A tumor cell-derived autocrine motility factor (AMF) was identified by its ability to induce the directed and random cell locomotion of the (self-)producing cells [4,5]. AMF was detected in the urine of patients with bladder carcinomas, potentially allowing the development of prognostic and/or diagnostic markers for bladder carcinomas [6].…”

Molecular Mechanisms and Pathways in Bladder Cancer Development and Progression

“…70 Using immunohistochemistry, increased microvascular density as a surrogate for angiogenesis has been found to be associated with tumor progression and decreased overall survival in BC patients. 71 Furthermore, increased urinary excretion of b-FGF, 70 angiogenic factors such as autocrine motility factor (AMF), 72 AMF receptor, 73 and hyaluronic acid and its degradation products 74 have been found in BC patients and have been proposed as means of detection and tumor monitoring.…”

The Role of Molecular Mechanisms in the Development of Bladder Carcinoma: Review

“…Ay rı ca di ğer an ji yo ge nik fak tör ler olan otok rin ha re ket li lik fak tö rü (AMF), 107 AMF re sep tö rü, 108 sik lo ok si je naz-2 (COX-2), hya lü ro nik asit ve bunla rın par ça lan ma ürün le ri nin 109 üri ner sa lı nı mı, me sa ne kan ser li has ta lar da art mak ta dır. Bu ne denle sö zü edi len bu fak tör le rin tes pit edil me si, tü mö -rün ta ki bin de önem li ola ca ğı nı dü şün dür mek te dir.…”