MATRIX METALLOPROTEINASE-1 IS INDUCED BY EPIDERMAL GROWTH-FACTOR IN HUMAN BLADDER-TUMOR CELL-LINES AND IS DETECTABLE IN URINE OF PATIENTS WITH BLADDER-TUMORS

The matrix metalloproteinases are a family of enzymes that degrade the extracellular matrix and are considered to be important in tumour inv asion and metastasis, The effect of epidermal growth factor (EGF) on m atrix metalloproteinase-1 (MMP1) production in two human bladder tumou r cell lines, RT112 and RT4, has been investigated. In the RT112 cell line, an increase in MMP1 mRNA levels was found after a 6-h incubation with EGF, and this further increased to 20-fold that of control level s at 24- and 48-h treatment with 50 ng ml(-1) of EGF, MMP2 mRNA levels remained constant over this time period, whereas in the RT4 cells no MMP2 transcripts were detectable, but MMPI transcripts again increased with 24- and 48-h treatment with 50 ng ml(-1) of EGF, MMP1 protein co ncentration in the conditioned medium from both cell lines increased w ith 24- and 48-h treatment of the cells and the total MMP1 was higher in the medium than the cells, demonstrating that the bladder tumour ce ll lines synthesize and secrete MMP1 protein after continuous stimulat ion with EGF, MMP1 protein was detected in urine from patients with bl adder rumours, with a significant increase in concentration with incre ased stage and grade of tumour. MMPI urine concentrations may therefor e be a useful prognostic indicator for bladder tumour progression.