URINARY LEVELS OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 CORRELATE WITH TUMOR STAGE AND GRADE IN PATIENTS WITH BLADDER-CANCER

Objective To determine if the chemokine monocyte chemo-attractant prot ein-1 (MCP-1) is produced locally in patients with bladder cancer and to analyse a possible correlation between tumour stage, grade and meta static spread, and the urinary and systemic levels of MCP-1. Patients, subjects and methods Urine and serum samples were obtained from 60 pa tients with bladder cancer and 20 control subjects. Tumour stage, grad e, metastasis and nodal status were assessed, MCP-1 levels in serum an d 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 tum our stage, grade and distant metastasis was highly significant, Patien ts with stage T2-T4 bladder cancer had three to fourfold higher mean M CP-1 concentrations (pg/mL) in their urine than those with T1 stage tu mours or than the controls (controls 260; T1 359, T2 967: T3 917; T4 1 829: P < 0.005). A tumour grade of > GI and the existence of distant m etastasis (M1) also correlated significantly with higher urinary MCP-1 levels (GI 373; GII 661; GIII 1111; MO 644; M1 1379; P < 0.05). No di fferences in circulating serum MCP-1 level were detected between contr ols and patients. The low-grade (GI) RT4 bladder cancer cell line prod uced only traces of MCP-1, which did not change under nutritional stre ss: in contrast, the highly malignant T24 bladder cancer cell line (GI II) spontaneously secreted large amounts of MCP-1 (approximate to 7000 pg/mL) which increased under nutritive stress to 13 000 pg/mL. Conclu sion MCP-1, as a potent monocyte chemoattractant to tumour sites, is p robably 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 mo nocyte/macrophage infiltrate possibly facilitates tumour neovasculariz ation and tissue invasion. Therefore, MCP-1 levels in the urine of pat ients with bladder cancer may be a prognostic marker for the natural c ourse of the disease, and modulation of this chemokine might be a futu re therapeutic approach for adjuvant treatment of bladder cancer.