Urinary levels of monocyte chemo-attractant protein-1 correlate with tumour stage and grade in patients with bladder cancer

Abstract

Objective: To determine if the chemokine monocyte chemo-attractant protein-1 (MCP-1) is produced locally in patients with bladder cancer and to analyse a possible correlation between tumour stage, grade and metastatic spread, and the urinary and systemic levels of MCP-1. PATIENTS SUBJECTS AND METHODS: Urine and serum samples were obtained from 60 patients with bladder cancer and 20 control subjects. Tumour stage, grade, metastasis and nodal status were assessed. MCP-1 levels in serum and urine were determined using a sandwich enzyme-linked immunosorbent assay. Two transitional cell cancer cell lines (grade I and grade III) were analysed for MCP-1 production under normal and nutritive-stress cell culture.

Results: The correlation of urinary MCP-1 levels with tumour stage, grade and distant metastasis was highly significant. Patients with stage T2-T4 bladder cancer had three to fourfold higher mean MCP-1 concentrations (pg/mL) in their urine than those with T1 stage tumours or than the controls (controls 260; T1 359; T2 967; T3 917; T4 1829; P < 0.005). A tumour grade of > GI and the existence of distant metastasis (M1) also correlated significantly with higher urinary MCP-1 levels (GI 373; GII 661; GIII 1111; M0 644; M1 1379; P < 0.05). No differences in circulating serum MCP-1 level were detected between controls and patients. The low-grade (GI) RT4 bladder cancer cell line produced only traces of MCP-1, which did not change under nutritional stress; in contrast, the highly malignant T24 bladder cancer cell line (GIII) spontaneously secreted large amounts of MCP-1 (approximately 7000 pg/mL) which increased under nutritive stress to 13,000 pg/mL.

Conclusion: MCP-1, as a potent monocyte chemo-attractant to tumour sites, is probably produced by bladder cancer cells; MCP-1 levels in the vicinity of the tumour (i.e. urine) correlate significantly with TNM stage and grade. As has already been shown in other neoplasms, the resulting monocyte/macrophage infiltrate possibly facilitates tumour neovascularization and tissue invasion. Therefore, MCP-1 levels in the urine of patients with bladder cancer may be a prognostic marker for the natural course of the disease, and modulation of this chemokine might be a future therapeutic approach for adjuvant treatment of bladder cancer.