The expression of urokinase-related genes in superficial and invasive transitional cell carcinoma

Tumor invasion and metastasis is mediated in part by proteolytic enzymes including urokinase plasminogen activator (uPA). The object of this study was to quantitate the molecular expression of urokinase plasminogen activator-related components in human superficial and invasive transitional cell carcinoma tumors (TCC), as well as parental and invasive variant TCC cell lines. We examined 15 invasive and 14 superficial TCC tumors (from a total of 29 patients) and six bladder carcinoma cell lines for the steady state mRNA levels of uPA, the uPA receptor and uPA inhibitor-1 by quantitative RT-PCR normalized to the L7 ribosomal transcript (a housekeeping gene). Transcript levels were expressed in a ratio to the L7 housekeeping transcript. There was a three fold increase in uPA expression in invasive lesions compared to superficial tumors (p < 0.003). In addition, there was a concordant 2.7 fold increase in the uPA receptor transcript in invasive TCC (p < 0.008). However, there was no significant difference in the steady state levels of the PAI-1 mRNA between invasive and superficial tumors. Transcript levels for the urokinase-related genes were similar between normal mucosa and superficial tumors. Cultured cells (parental and invasive variants) were found to express higher levels of the three uPA-related genes overall. Invasive TCC cells selected by serial passage through a Boyden chamber demonstrated higher levels of uPA, uPA receptor and PAI-1 than parental cells (p < 0.05). These data from the human tumor specimens suggest that increased uPA and uPAr expression may be component of the invasive phenotype of TCC lesions.